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Volume 27,Issue 5,2020 Table of Contents
2020, 27(5):469-476.
DOI: 10.3872/j.issn.1007-385X.2020.05.001
Abstract:
The efficacy and prognosis of human epidermal growth factor receptor 2 (HER2) positive breast cancer patients have been significantly improved with the development and wide application of anti-tumor drugs against HER2. The results of PEONY research once again established the status of the double-target treatment mode of pertuzumab+trastuzumab in the field of neoadjuvant therapy.Based on the two studies of TRYPHAENA and TRAIN-2, paclitaxel plus platinum should be the first choice chemotherapy scheme for anti HER2 double-target therapy, and the treatment course of 6 cycles is preferred. According to the consensus of neoadjuvant therapy experts in China and the latest follow-up results of adjuvant APT study, the neoadjuvant therapy is more suitable for patients with a tumor diameter of more than 3 cm and/or positive lymph nodes metastasis; T-DM1 should be the first choice of adjuvant therapy in patients, who didn’t obtain pCR after neoadjuvant treatment, and whether the double-target adjuvant mode of pertuzumab plus trastuzumab is suitable depends on follow-up of the PEONY study. Low-risk patients with small tumors (<3 cm) and without lymph node metastasis may consider omitting neoadjuvant therapy but adopt direct surgery followed by postoperative adjuvant therapy with trastuzumab plus paclitaxel. The regimen of trastuzumab+pertuzumab combined with taxanes is still the standard first line treatment of late stage HER2+ patients; for Chinese patients, pyrotinib combined with capecitabine can be used as the second line optimization,and T-DM1 can be used as the third line and posterior line selection; when trastuzumab, pertuzumab and T-DM1 fail the treatment,DS-8201 becomes a new selection mode. Combined treatment mode of tucatinib plus trastuzumab and capecitabine can be considered in late stage HER2+ patients with brain metastases.
The efficacy and prognosis of human epidermal growth factor receptor 2 (HER2) positive breast cancer patients have been significantly improved with the development and wide application of anti-tumor drugs against HER2. The results of PEONY research once again established the status of the double-target treatment mode of pertuzumab+trastuzumab in the field of neoadjuvant therapy.Based on the two studies of TRYPHAENA and TRAIN-2, paclitaxel plus platinum should be the first choice chemotherapy scheme for anti HER2 double-target therapy, and the treatment course of 6 cycles is preferred. According to the consensus of neoadjuvant therapy experts in China and the latest follow-up results of adjuvant APT study, the neoadjuvant therapy is more suitable for patients with a tumor diameter of more than 3 cm and/or positive lymph nodes metastasis; T-DM1 should be the first choice of adjuvant therapy in patients, who didn’t obtain pCR after neoadjuvant treatment, and whether the double-target adjuvant mode of pertuzumab plus trastuzumab is suitable depends on follow-up of the PEONY study. Low-risk patients with small tumors (<3 cm) and without lymph node metastasis may consider omitting neoadjuvant therapy but adopt direct surgery followed by postoperative adjuvant therapy with trastuzumab plus paclitaxel. The regimen of trastuzumab+pertuzumab combined with taxanes is still the standard first line treatment of late stage HER2+ patients; for Chinese patients, pyrotinib combined with capecitabine can be used as the second line optimization,and T-DM1 can be used as the third line and posterior line selection; when trastuzumab, pertuzumab and T-DM1 fail the treatment,DS-8201 becomes a new selection mode. Combined treatment mode of tucatinib plus trastuzumab and capecitabine can be considered in late stage HER2+ patients with brain metastases.
2020, 27(5):477-486.
DOI: 10.3872/j.issn.1007-385X.2020.05.002
Abstract:
Objective: To investigate the effects of miR-625 and Resistin on the proliferation, invasion and migration of NSCLC cells as well as the growth of transplanted tumors in nude mice and their possible mechanisms. Methods: qPCR was used to detect the expression of miR-625 and Resistin in 80 pairs of NSCLC and corresponding para-cancerous tissues (specimens collected from NSCLC patients who were surgically treated in Xinjiang Uygur Autonomous Region People’s Hospital from March 2018 to October 2019) and four cell lines. Bioinformatics was adopted to predict the targeting relationship between miR-625 and Resistin, which was then verified by Dual luciferase gene reporter experiment. Overexpression or inhibition of miR-625 and Resistin in NSCLC cells was achieved with lipofection transfection technology, and the experimental cells were divided into miR-625 mimic group, miR-625 inhibitor group, si-Resisitin group, miR-625 inhibitor+si-Resisitin group and NC group. The effects of miR-625 and Resistin on proliferation, invasion and migration of NSCLC cells were detected by CCK-8, Transwell and Scratch test, respectively. Western blotting was used to detect the effects of miR-625 and Resistin on the expressions of PI3K/AKT/Snail pathway proteins related with EMT in NSCLC cells. A549 cell transplanted tumor model was constructed in nude mice to observe the effect of miR-625 and Resistin on the growth of xenografts. Results: Compared with para-cancerous tissues, miR-625 showed low expression while Resistin showed high expression in NSCLC tissues and four cell lines (both P<0.01), and the two were negatively correlated (r=-0.7183,P<0.01). The expression of Resistin was related to the degree of NSCLC differentiation, clinical stage and lymph node metastasis. Resistin was a target gene of miR-625. Compared with the Blank group and NC group, the proliferation, invasion and migration of NSCLC cell lines A549 and H226, as well as the growth of transplanted tumors in nude mice in the miR-625 mimic group and the si-Resistin group were significantly reduced (all P<0.05), while those indicators in the miR-625 inhibitor group were significantly improved (all P<0.05); However, co-transfection of miR-625 inhibitor and si-Resistin significantly reversed the effect of miR-625 inhibitor on above indicators (all P<0.05); And there was no significant difference between NC group and miR-625 inhibitor+si-Resistin group (all P>0.05). The protein expressions of p-AKT, p-PI3K, Snail, Twist1 and Vimentin also showed the same trend (all P<0.05), while the expression of E-cadherin protein changed in the opposite direction (P<0.05). Conclusion: miR-625 is lowly expressed in NSCLC tissues and cell lines, which can negatively regulate Resistin expression to inhibit the proliferation, invasion and migration of NSCLC cells and the growth of transplanted tumors in nude mice. The mechanism may be related to the PI3K/AKT/Snail signaling pathway.
Objective: To investigate the effects of miR-625 and Resistin on the proliferation, invasion and migration of NSCLC cells as well as the growth of transplanted tumors in nude mice and their possible mechanisms. Methods: qPCR was used to detect the expression of miR-625 and Resistin in 80 pairs of NSCLC and corresponding para-cancerous tissues (specimens collected from NSCLC patients who were surgically treated in Xinjiang Uygur Autonomous Region People’s Hospital from March 2018 to October 2019) and four cell lines. Bioinformatics was adopted to predict the targeting relationship between miR-625 and Resistin, which was then verified by Dual luciferase gene reporter experiment. Overexpression or inhibition of miR-625 and Resistin in NSCLC cells was achieved with lipofection transfection technology, and the experimental cells were divided into miR-625 mimic group, miR-625 inhibitor group, si-Resisitin group, miR-625 inhibitor+si-Resisitin group and NC group. The effects of miR-625 and Resistin on proliferation, invasion and migration of NSCLC cells were detected by CCK-8, Transwell and Scratch test, respectively. Western blotting was used to detect the effects of miR-625 and Resistin on the expressions of PI3K/AKT/Snail pathway proteins related with EMT in NSCLC cells. A549 cell transplanted tumor model was constructed in nude mice to observe the effect of miR-625 and Resistin on the growth of xenografts. Results: Compared with para-cancerous tissues, miR-625 showed low expression while Resistin showed high expression in NSCLC tissues and four cell lines (both P<0.01), and the two were negatively correlated (r=-0.7183,P<0.01). The expression of Resistin was related to the degree of NSCLC differentiation, clinical stage and lymph node metastasis. Resistin was a target gene of miR-625. Compared with the Blank group and NC group, the proliferation, invasion and migration of NSCLC cell lines A549 and H226, as well as the growth of transplanted tumors in nude mice in the miR-625 mimic group and the si-Resistin group were significantly reduced (all P<0.05), while those indicators in the miR-625 inhibitor group were significantly improved (all P<0.05); However, co-transfection of miR-625 inhibitor and si-Resistin significantly reversed the effect of miR-625 inhibitor on above indicators (all P<0.05); And there was no significant difference between NC group and miR-625 inhibitor+si-Resistin group (all P>0.05). The protein expressions of p-AKT, p-PI3K, Snail, Twist1 and Vimentin also showed the same trend (all P<0.05), while the expression of E-cadherin protein changed in the opposite direction (P<0.05). Conclusion: miR-625 is lowly expressed in NSCLC tissues and cell lines, which can negatively regulate Resistin expression to inhibit the proliferation, invasion and migration of NSCLC cells and the growth of transplanted tumors in nude mice. The mechanism may be related to the PI3K/AKT/Snail signaling pathway.
2020, 27(5):487-495.
DOI: 10.3872/j.issn.1007-385X.2020.05.003
Abstract:
Objective: To study the effect of Notch4 signaling pathway on the self-renewal capacity of cancer stem cells (CSCs) of oral squamous cell carcinoma PJ15 and PJ41 cells and its mechanism. Methods: The expression of Notch4 gene in head and neck tumors was analyzed using TCGA database. 2 μmol/L cisplatin was used to treat oral squamous cell carcinoma PJ15 and PJ41 cells for 48 h,following with the treatment of Notch pathway inhibitor DAPT for 24 h. Flow cytometry was used to detect the ratio of CSCs, Western blotting and qPCR were used to detect the expressions of CSCs markers (Sox2, Bmi-1, Oct4, Nanog) and downstream genes in Notch4 signaling pathway (JAG1, HEY1, HEY2, HES1, HES2, DLL4, etc.). Notch4 was knocked down by siRNA technology. Notch4 was silenced with siRNA technology. Western blotting and qPCR were used to detect the effect of si-Notch4 and cisplatin on the expression level of CSCs markers. The stem cell pelleting test was used to detect the self-renewal ability of CSCs. Results: Notch4 gene was highly expressed in head and neck tumor tissues (P=0.046). After cisplatin treatment, compared with the control group, expressions of NICD4 and CSCs markers (Sox2, Bmi-1, Oct4, Nanog) as well as downstream genes of Notch4 signaling pathway (JAG1, HEY1, HEY2,HES1, HES2, DLL4, etc.) increased significantly (all P<0.05), and the proportion of ALDH1 positive cells increased significantly (P<0.05); with the further addition of DAPT, the expressions of the above genes decreased significantly (P<0.05 or P<0.01). After knocking down Notch4, compared with the control group, the size and number of spheres of PJ15 cells [1.33±0.47] vs [8.00±0.82],P<0.01) and PJ41 cells ([1.00±0.82] vs [7.67±1.25], P<0.01) were significantly lower than that of the control group; after the addition of 2 μmol/L DDP for 24 h, there was no significant difference in the expressions of Nanog and Bmi-1 gene between si-Notch4 group and control group. Conclusion: Activation of Notch4 signaling pathway can enhance the self-renewal ability of CSCs in oral squamous cell carcinoma PJ15 and PJ41 cells.
Objective: To study the effect of Notch4 signaling pathway on the self-renewal capacity of cancer stem cells (CSCs) of oral squamous cell carcinoma PJ15 and PJ41 cells and its mechanism. Methods: The expression of Notch4 gene in head and neck tumors was analyzed using TCGA database. 2 μmol/L cisplatin was used to treat oral squamous cell carcinoma PJ15 and PJ41 cells for 48 h,following with the treatment of Notch pathway inhibitor DAPT for 24 h. Flow cytometry was used to detect the ratio of CSCs, Western blotting and qPCR were used to detect the expressions of CSCs markers (Sox2, Bmi-1, Oct4, Nanog) and downstream genes in Notch4 signaling pathway (JAG1, HEY1, HEY2, HES1, HES2, DLL4, etc.). Notch4 was knocked down by siRNA technology. Notch4 was silenced with siRNA technology. Western blotting and qPCR were used to detect the effect of si-Notch4 and cisplatin on the expression level of CSCs markers. The stem cell pelleting test was used to detect the self-renewal ability of CSCs. Results: Notch4 gene was highly expressed in head and neck tumor tissues (P=0.046). After cisplatin treatment, compared with the control group, expressions of NICD4 and CSCs markers (Sox2, Bmi-1, Oct4, Nanog) as well as downstream genes of Notch4 signaling pathway (JAG1, HEY1, HEY2,HES1, HES2, DLL4, etc.) increased significantly (all P<0.05), and the proportion of ALDH1 positive cells increased significantly (P<0.05); with the further addition of DAPT, the expressions of the above genes decreased significantly (P<0.05 or P<0.01). After knocking down Notch4, compared with the control group, the size and number of spheres of PJ15 cells [1.33±0.47] vs [8.00±0.82],P<0.01) and PJ41 cells ([1.00±0.82] vs [7.67±1.25], P<0.01) were significantly lower than that of the control group; after the addition of 2 μmol/L DDP for 24 h, there was no significant difference in the expressions of Nanog and Bmi-1 gene between si-Notch4 group and control group. Conclusion: Activation of Notch4 signaling pathway can enhance the self-renewal ability of CSCs in oral squamous cell carcinoma PJ15 and PJ41 cells.
2020, 27(5):496-500.
DOI: 10.3872/j.issn.1007-385X.2020.05.004
Abstract:
Objective：To investigate the effect of miRNA-325-3p and its target gene cytokeratin 13 (CK13) on the radio-sensitivity of nasopharyngeal carcinoma cell line CNE1. Methods：The potential target gene of miRNA-325-3p was predicted by three databases:miRBase, Targetscan and microcosm, and verified by Double luciferase activity assay. QPCR was used to detect the expression levels of miRNA-325-3p and its target gene in nasopharyngeal carcinoma cell line CNE1 under different radiation doses; To verify the changes in radio-sensitivity of nasopharyngeal carcinoma cells, colony formation assay, Flow cytometery and MTT were used to observe the clone formation, apoptosis and cell viability of CNE1 cells after overexpression of miRNA-325-3p and knockdown of CK13 under different radiation doses, respectively. Results：CK13 was confirmed as a potential target gene of miRNA-325-3p. After radiotherapy, the expression level of miRNA-325-3p in CNE1 cell was significantly increased, while the expression level of CK13 was decreased (all P<0.05); up-regulation of miRNA-325-3p expression and silence of CK13 gene increased cell survival rate (upregulation of miRNA-325-3p: [60.14±3.55]% vs [19.23±3.42]%, t=14.37, P<0.01; silence of CK13: [76.15±5.13]% vs [28.53±3.68]%, t=13.06, P<0.01)and colony formation rate, and decreased apoptosis rate (upregulation of miRNA-325-3p: [27.95±2.67]% vs [51.68±3.47]%, t=9.39,P<0.01; silence of CK13: [20.31±2.62]% vs [38.14±3.83]%, t=6.66, P<0.01). Conclusion：miRNA-325-3p can reduce the sensitivity of nasopharyngeal carcinoma cell line CNE1 to radiotherapy by down-regulating the target gene CK13.
Objective：To investigate the effect of miRNA-325-3p and its target gene cytokeratin 13 (CK13) on the radio-sensitivity of nasopharyngeal carcinoma cell line CNE1. Methods：The potential target gene of miRNA-325-3p was predicted by three databases:miRBase, Targetscan and microcosm, and verified by Double luciferase activity assay. QPCR was used to detect the expression levels of miRNA-325-3p and its target gene in nasopharyngeal carcinoma cell line CNE1 under different radiation doses; To verify the changes in radio-sensitivity of nasopharyngeal carcinoma cells, colony formation assay, Flow cytometery and MTT were used to observe the clone formation, apoptosis and cell viability of CNE1 cells after overexpression of miRNA-325-3p and knockdown of CK13 under different radiation doses, respectively. Results：CK13 was confirmed as a potential target gene of miRNA-325-3p. After radiotherapy, the expression level of miRNA-325-3p in CNE1 cell was significantly increased, while the expression level of CK13 was decreased (all P<0.05); up-regulation of miRNA-325-3p expression and silence of CK13 gene increased cell survival rate (upregulation of miRNA-325-3p: [60.14±3.55]% vs [19.23±3.42]%, t=14.37, P<0.01; silence of CK13: [76.15±5.13]% vs [28.53±3.68]%, t=13.06, P<0.01)and colony formation rate, and decreased apoptosis rate (upregulation of miRNA-325-3p: [27.95±2.67]% vs [51.68±3.47]%, t=9.39,P<0.01; silence of CK13: [20.31±2.62]% vs [38.14±3.83]%, t=6.66, P<0.01). Conclusion：miRNA-325-3p can reduce the sensitivity of nasopharyngeal carcinoma cell line CNE1 to radiotherapy by down-regulating the target gene CK13.
2020, 27(5):501-507.
DOI: 10.3872/j.issn.1007-385X.2020.05.005
Abstract:
Objective:To explore the targeting relationship between long-chain noncoding RNA HOXA-AS2 (lncRNA HOXA-AS2)and microRNA-520a-3p (miR-520a-3p) and their effects on the proliferation, migration and invasion of ovarian cancer SKOV3 cells.Methods：qPCR was used to detect the expression levels of lncRNA HOXA-AS2 and miR-520a-3p in various ovarian cancer cell lines (SKOV3, HO8910, OVCAR3 cells) and normal ovarian epithelial cell line HOSE. Bioinformatics methods were used to predict the targeting relationship between HOXA-AS2 and miR-520a-3p, which was then verified by Dual luciferase reporter gene assay.si-HOXA-AS2, miR-520a-3p mimic, anti-miR-520a-3p and corresponding control fragments were transfected into SKOV3 cells separately or in combination. MTT, Transwell and Western blotting were used to detect the proliferation, migration, invasion and expressions of related proteins (CyclinD1, p21, p27, MMP-2, MMP-9, MMP-14) of SKOV3 cells in each group. Results: Compared with HOSE cells, HOXA-AS2 was over-expressed while miR-520a-3p was under-expressed in ovarian cancer cell lines (all P<0.05).HOXA-AS2 could targetedly down-regulate the expression of miR-520a-3p. Compared with the NC group, the proliferation, migration and invasion of SKOV3 cells in the si-HOXA-AS2 and miR-520a-3p mimics groups were significantly reduced (all P<0.01),and the protein expressions of p21 and p27 were significantly increased, while protein expressions of CyclinD1, MMP-2, MMP-9,MMP-14 were significantly reduced (all P<0.01). The proliferation, migration and invasion of SKOV3 cells in the si-HOXA-AS2+antimiR-520a-3p group were significantly enhanced compared with those in si-HOXA-AS2 and si-HOXA-AS2+anti-miR-NC groups (all P<0.05). Conclusion: lncRNA HOXA-AS2 enhances the proliferation, migration and invasion of ovarian cancer SKOV3 cells by targetedly inhibiting the expression of miR-520a-3p.
Objective:To explore the targeting relationship between long-chain noncoding RNA HOXA-AS2 (lncRNA HOXA-AS2)and microRNA-520a-3p (miR-520a-3p) and their effects on the proliferation, migration and invasion of ovarian cancer SKOV3 cells.Methods：qPCR was used to detect the expression levels of lncRNA HOXA-AS2 and miR-520a-3p in various ovarian cancer cell lines (SKOV3, HO8910, OVCAR3 cells) and normal ovarian epithelial cell line HOSE. Bioinformatics methods were used to predict the targeting relationship between HOXA-AS2 and miR-520a-3p, which was then verified by Dual luciferase reporter gene assay.si-HOXA-AS2, miR-520a-3p mimic, anti-miR-520a-3p and corresponding control fragments were transfected into SKOV3 cells separately or in combination. MTT, Transwell and Western blotting were used to detect the proliferation, migration, invasion and expressions of related proteins (CyclinD1, p21, p27, MMP-2, MMP-9, MMP-14) of SKOV3 cells in each group. Results: Compared with HOSE cells, HOXA-AS2 was over-expressed while miR-520a-3p was under-expressed in ovarian cancer cell lines (all P<0.05).HOXA-AS2 could targetedly down-regulate the expression of miR-520a-3p. Compared with the NC group, the proliferation, migration and invasion of SKOV3 cells in the si-HOXA-AS2 and miR-520a-3p mimics groups were significantly reduced (all P<0.01),and the protein expressions of p21 and p27 were significantly increased, while protein expressions of CyclinD1, MMP-2, MMP-9,MMP-14 were significantly reduced (all P<0.01). The proliferation, migration and invasion of SKOV3 cells in the si-HOXA-AS2+antimiR-520a-3p group were significantly enhanced compared with those in si-HOXA-AS2 and si-HOXA-AS2+anti-miR-NC groups (all P<0.05). Conclusion: lncRNA HOXA-AS2 enhances the proliferation, migration and invasion of ovarian cancer SKOV3 cells by targetedly inhibiting the expression of miR-520a-3p.
2020, 27(5):508-514.
DOI: 10.3872/j.issn.1007-385X.2020.05.006
Abstract:
Objective: To investigate the mechanisms of carnitine palmitoyltransferase 1c (CPT1c) expression to affect the proliferation and apoptosis of human thyroid papillary cancer B-CPAP cells through the AMP-dependent/activated protein kinase (AMPK) pathway in the low glucose and hypoxic conditions. Methods: Firstly, human thyroid papillary carcinoma B-CPAP cells were cultured under normal condition or low glucose and hypoxic condition respectively, followed with the treatment of AMPK inhibitor compound C.Western blotting was used to detect the expressions of AMPK, p-AMPK, peroxisome proliferator-activated receptor α (PPARα) and CPT1c; the proliferation and apoptosis were detected by CCK-8 and Flow cytometry, respectively. Then PPARα-siRNA was synthesized and transfected into B-CPAP cells to knock down PPARα, and then the cells were cultured under normal or low glucose and hypoxic condition respectively. Above indicators were also detected to verify the regulation of PPARα on CPT1c. Finally, the human luciferase reporter plasmid containing CPT1c gene promoter was constructed, and the effect of PPARα on the activity of CPT1c promoter luciferase activity was observed by immunofluorescence. Results: The expressions of AMPK, p-AMPK, PPARα and CPT1c were significantly increased in B-CPAP cells under low glucose and hypoxia condition (P<0.05 or P<0.01), while cell proliferation and apoptosis rate did not change significantly (P>0.05). After the treatment of AMPK inhibitor compound C, the expressions of p-AMPK, PPARα and CPT1c in low glucose and hypoxia group were significantly decreased (P<0.05 or P<0.01), the inhibitory rate on cell proliferation and apoptosis rate were significantly increased (P<0.05). However, the change range was smaller than that in the normal culture + compound C group (P<0.05). After PPARα knockdown, the expressions of AMPK, p-AMPK, PPARα and CPT1c in cancer cells cultured under normal conditions were significantly decreased (P<0.05 or P<0.01), and the inhibitory rate on cell proliferation and apoptosis rate were significantly increased (P<0.05). While under low glucose and hypoxia condition, the expression of CPT1c in cells after transfection was significantly decreased (P<0.05), and the inhibition rate on cell proliferation and the apoptosis rate were significantly increased (P<0.05); However, the change range was still lower than that of normal condition group after transfection (P<0.05). After PPARα overexpression,the ratio of fluorescence in the empty vector group was not significantly different from that of the blank group (P>0.05),and the ratio of fluorescence was significantly increased in PPARα over-expression group (P<0.05). Conclusions: AMPK can increase the expression of PPAR α to promote the expression of CPT1c in thyroid cancer B-CPAP cells under low glucose and hypoxia conditions, thereby inhibiting cell apoptosis and maintaining cell proliferation ability.
Objective: To investigate the mechanisms of carnitine palmitoyltransferase 1c (CPT1c) expression to affect the proliferation and apoptosis of human thyroid papillary cancer B-CPAP cells through the AMP-dependent/activated protein kinase (AMPK) pathway in the low glucose and hypoxic conditions. Methods: Firstly, human thyroid papillary carcinoma B-CPAP cells were cultured under normal condition or low glucose and hypoxic condition respectively, followed with the treatment of AMPK inhibitor compound C.Western blotting was used to detect the expressions of AMPK, p-AMPK, peroxisome proliferator-activated receptor α (PPARα) and CPT1c; the proliferation and apoptosis were detected by CCK-8 and Flow cytometry, respectively. Then PPARα-siRNA was synthesized and transfected into B-CPAP cells to knock down PPARα, and then the cells were cultured under normal or low glucose and hypoxic condition respectively. Above indicators were also detected to verify the regulation of PPARα on CPT1c. Finally, the human luciferase reporter plasmid containing CPT1c gene promoter was constructed, and the effect of PPARα on the activity of CPT1c promoter luciferase activity was observed by immunofluorescence. Results: The expressions of AMPK, p-AMPK, PPARα and CPT1c were significantly increased in B-CPAP cells under low glucose and hypoxia condition (P<0.05 or P<0.01), while cell proliferation and apoptosis rate did not change significantly (P>0.05). After the treatment of AMPK inhibitor compound C, the expressions of p-AMPK, PPARα and CPT1c in low glucose and hypoxia group were significantly decreased (P<0.05 or P<0.01), the inhibitory rate on cell proliferation and apoptosis rate were significantly increased (P<0.05). However, the change range was smaller than that in the normal culture + compound C group (P<0.05). After PPARα knockdown, the expressions of AMPK, p-AMPK, PPARα and CPT1c in cancer cells cultured under normal conditions were significantly decreased (P<0.05 or P<0.01), and the inhibitory rate on cell proliferation and apoptosis rate were significantly increased (P<0.05). While under low glucose and hypoxia condition, the expression of CPT1c in cells after transfection was significantly decreased (P<0.05), and the inhibition rate on cell proliferation and the apoptosis rate were significantly increased (P<0.05); However, the change range was still lower than that of normal condition group after transfection (P<0.05). After PPARα overexpression,the ratio of fluorescence in the empty vector group was not significantly different from that of the blank group (P>0.05),and the ratio of fluorescence was significantly increased in PPARα over-expression group (P<0.05). Conclusions: AMPK can increase the expression of PPAR α to promote the expression of CPT1c in thyroid cancer B-CPAP cells under low glucose and hypoxia conditions, thereby inhibiting cell apoptosis and maintaining cell proliferation ability.
2020, 27(5):515-521.
DOI: 10.3872/j.issn.1007-385X.2020.05.007
Abstract:
Objective: To explore the effect of circ_0001429 on proliferation and apoptosis of bladder cancer cells by regulating miR-139-5p/TGF-interacting factor 1（TGIF1）axis. Methods: The expression of circ_0001429 in bladder cancer cell lines SW780, T24,5637 and human bladder epithelial SV-HUC-1 cells were detected by RT-qPCR. Targeted regulatory relationship between circ_0001429 and miR-139-5p as well as miR-139-5p and TGIF1 was measured by Dual luciferase reporter gene assay. T24 cells were divided into NC group, sh-circ_0001429 group, miR-139-5p mimics group, sh-TGIF1 group, pcDNA-circ_0001429+sh-TGIF1 group, miR-139-5p mimics+pcDNA-TGIF1 group and sh-circ_0001429+miR-139-5p inhibitor group. Western blotting was used to detect the expression level of TGIF1 in each group. CCK-8 method, Transwell experiment and Flow cytometry were used to detect the effects of circ_0001429, miR-139-5p and TGIF1 on proliferation, invasion, migration and apoptosis of T24 cells, respectively. Results: Circ_0001429 was highly expressed in three bladder cancer cell lines (P<0.01). Knockdown of circ_0001429 significantly inhibited proliferation,invasion and migration of T24 cells while promoted the level of cell apoptosis (P<0.05 or P<0.01). The results of Dual luciferase reporter gene assay confirmed that there is a targeting relationship between circ_0001429 and miR-139-5p as well as between miR-139-5p and TGIF1. Overexpression of miR-139-5p significantly inhibited the proliferation, invasion and migration of T24 cells while promoted the level of cell apoptosis (all P<0.01). Recovery experiments further confirmed that the competitive binding of circ_0001429 and TGIF1 to miR-139-5p promoted the proliferation, invasion and migration of T24 cells while inhibited the level of cell apoptosis (all P<0.01). Conclusion: Circ_0001429 promotes proliferation, invasion and migration and inhibits apoptosis of bladder cancer T24 cells by competing with TGIF1 to bind to miR-139-5p.
Objective: To explore the effect of circ_0001429 on proliferation and apoptosis of bladder cancer cells by regulating miR-139-5p/TGF-interacting factor 1（TGIF1）axis. Methods: The expression of circ_0001429 in bladder cancer cell lines SW780, T24,5637 and human bladder epithelial SV-HUC-1 cells were detected by RT-qPCR. Targeted regulatory relationship between circ_0001429 and miR-139-5p as well as miR-139-5p and TGIF1 was measured by Dual luciferase reporter gene assay. T24 cells were divided into NC group, sh-circ_0001429 group, miR-139-5p mimics group, sh-TGIF1 group, pcDNA-circ_0001429+sh-TGIF1 group, miR-139-5p mimics+pcDNA-TGIF1 group and sh-circ_0001429+miR-139-5p inhibitor group. Western blotting was used to detect the expression level of TGIF1 in each group. CCK-8 method, Transwell experiment and Flow cytometry were used to detect the effects of circ_0001429, miR-139-5p and TGIF1 on proliferation, invasion, migration and apoptosis of T24 cells, respectively. Results: Circ_0001429 was highly expressed in three bladder cancer cell lines (P<0.01). Knockdown of circ_0001429 significantly inhibited proliferation,invasion and migration of T24 cells while promoted the level of cell apoptosis (P<0.05 or P<0.01). The results of Dual luciferase reporter gene assay confirmed that there is a targeting relationship between circ_0001429 and miR-139-5p as well as between miR-139-5p and TGIF1. Overexpression of miR-139-5p significantly inhibited the proliferation, invasion and migration of T24 cells while promoted the level of cell apoptosis (all P<0.01). Recovery experiments further confirmed that the competitive binding of circ_0001429 and TGIF1 to miR-139-5p promoted the proliferation, invasion and migration of T24 cells while inhibited the level of cell apoptosis (all P<0.01). Conclusion: Circ_0001429 promotes proliferation, invasion and migration and inhibits apoptosis of bladder cancer T24 cells by competing with TGIF1 to bind to miR-139-5p.
2020, 27(5):522-527.
DOI: 10.3872/j.issn.1007-385X.2020.05.008
Abstract:
Objective: To investigate the effects of salidroside on the proliferation, invasion and apoptosis of cervical squamous cell carcinoma C33A cells and explore its possible mechanism. Methods: C33A cells were divided into 4 groups: control group, low-dose group (salidroside 50 μg/mL), high-dose group (salidroside 150 μg/mL), and AG490 group (inhibitor of JAK2/STAT3 signaling pathway,50 μmol/L). Effects of salidroside and AG490 on the proliferation, invasion and apoptosis of C33A cells were detected by MTT method, EdU labeling experiment, Transwell assay, Rh123 staining and Flow cytometry, respectively. Western blotting was used to detect the effects of salidroside and AG490 on the expressions of JAK2/STAT3 pathway-related proteins (p-JAK2, p-STAT3) and apoptosis-related proteins (Bax, Bcl-2, caspase-3) in C33A cells. Result: Compared with the control group, the proliferation and DNA synthesis as well as the invasion of C33A cells in the low-dose group were significantly inhibited (all P<0.05), while the apoptosis was significantly enhanced (P<0.05); in the meanwhile, the fluorescence intensity of Rh123 was significantly reduced (all P<0.05) and the membrane structure of C33A cells were destroyed; moreover, the expressions of p-JAK2, p-STAT3 and Bcl-2 were significantly decreased while the expressions of Bax and caspase-3 were significantly increased (all P<0.05). Compared with the low-dose group, the effects of high-dose salidroside and AG490 on the proliferation, invasion, apoptosis and related protein expressions in C33A cells were more significant (all P<0.05), but there was no difference between the high-dose group and the AG490 group. Conclusion: Salidroside can inhibit the proliferation and invasion of C33A cells and promote cell apoptosis. Its mechanism may be related to inhibition of JAK2/STAT3 signaling pathway.
Objective: To investigate the effects of salidroside on the proliferation, invasion and apoptosis of cervical squamous cell carcinoma C33A cells and explore its possible mechanism. Methods: C33A cells were divided into 4 groups: control group, low-dose group (salidroside 50 μg/mL), high-dose group (salidroside 150 μg/mL), and AG490 group (inhibitor of JAK2/STAT3 signaling pathway,50 μmol/L). Effects of salidroside and AG490 on the proliferation, invasion and apoptosis of C33A cells were detected by MTT method, EdU labeling experiment, Transwell assay, Rh123 staining and Flow cytometry, respectively. Western blotting was used to detect the effects of salidroside and AG490 on the expressions of JAK2/STAT3 pathway-related proteins (p-JAK2, p-STAT3) and apoptosis-related proteins (Bax, Bcl-2, caspase-3) in C33A cells. Result: Compared with the control group, the proliferation and DNA synthesis as well as the invasion of C33A cells in the low-dose group were significantly inhibited (all P<0.05), while the apoptosis was significantly enhanced (P<0.05); in the meanwhile, the fluorescence intensity of Rh123 was significantly reduced (all P<0.05) and the membrane structure of C33A cells were destroyed; moreover, the expressions of p-JAK2, p-STAT3 and Bcl-2 were significantly decreased while the expressions of Bax and caspase-3 were significantly increased (all P<0.05). Compared with the low-dose group, the effects of high-dose salidroside and AG490 on the proliferation, invasion, apoptosis and related protein expressions in C33A cells were more significant (all P<0.05), but there was no difference between the high-dose group and the AG490 group. Conclusion: Salidroside can inhibit the proliferation and invasion of C33A cells and promote cell apoptosis. Its mechanism may be related to inhibition of JAK2/STAT3 signaling pathway.
2020, 27(5):528-533.
DOI: 10.3872/j.issn.1007-385X.2020.05.009
Abstract:
Objective: To investigate the influences of human lung adenocarcinoma PC-9 cells on tight junction proteins of blood brain barrier (BBB) under CXCR4/SDF-1 axis by establishing a model of BBB in vitro. Methods: The immortalized mouse brain microvascular endothelial Bends cells were used to establish a model of BBB in vitro by monolayer culture; Subsequently, transendothelial electric resistance (TEER) and fluorescein sodium permeability experiment were used to detect the function of in vitro BBB model and observe the effect of PC-9 cells on the function of BBB model, respectively. Western blotting was used to detect the effect of PC-9 cells on function of BBB model and expressions of endothelial tight junction proteins under the treatment of single or combined AMD3100 and SDF-1 (1 μg/ml AMD3100,100 ng/ml SDF-1, AMD3100+SDF-1). Transwell assay was used to detect the influence of CXCR4/SDF-1 axis on the ability of PC-9 cells transmigrating the cell layer of BBB model. Results: Monolayer culture of Bends cells can form tightly connected BBB with highTEER, which reached (182.13±5.19) Ω.cm2 at the 96 h; in the meanwhile, fluorescein sodium permeability experiment showed that BBB had significantly lower permeability than that of control group ([40.31±2.43]% vs [150.10±3.17]%, P<0.05). The TEER of BBB decreased to (46.7±4.35) Ω·cm2 after coculture with PC-9 cells for 24 h, and at the same time the sodium fluorescein permeability of BBB significantly increased than that of pre-treatment ([136.32±4.93]% vs [50.24±6.21]%, P<0.05).PC-9 cells up-regulated the expressions of tight junction proteins of Bends cells under the treatment of AMD3100 (P<0.05). The number of PC-9 cells transmigrating the BBB in AMD3100 treatment group was significantly lower than that of CON group (43±2 vs 81±2,P<0.05). Conclusion: AMD3100 can reduce the ability of PC-9 cells destroying the tight junction of the BBB model established in vitro by Bends cells.
Objective: To investigate the influences of human lung adenocarcinoma PC-9 cells on tight junction proteins of blood brain barrier (BBB) under CXCR4/SDF-1 axis by establishing a model of BBB in vitro. Methods: The immortalized mouse brain microvascular endothelial Bends cells were used to establish a model of BBB in vitro by monolayer culture; Subsequently, transendothelial electric resistance (TEER) and fluorescein sodium permeability experiment were used to detect the function of in vitro BBB model and observe the effect of PC-9 cells on the function of BBB model, respectively. Western blotting was used to detect the effect of PC-9 cells on function of BBB model and expressions of endothelial tight junction proteins under the treatment of single or combined AMD3100 and SDF-1 (1 μg/ml AMD3100,100 ng/ml SDF-1, AMD3100+SDF-1). Transwell assay was used to detect the influence of CXCR4/SDF-1 axis on the ability of PC-9 cells transmigrating the cell layer of BBB model. Results: Monolayer culture of Bends cells can form tightly connected BBB with highTEER, which reached (182.13±5.19) Ω.cm2 at the 96 h; in the meanwhile, fluorescein sodium permeability experiment showed that BBB had significantly lower permeability than that of control group ([40.31±2.43]% vs [150.10±3.17]%, P<0.05). The TEER of BBB decreased to (46.7±4.35) Ω·cm2 after coculture with PC-9 cells for 24 h, and at the same time the sodium fluorescein permeability of BBB significantly increased than that of pre-treatment ([136.32±4.93]% vs [50.24±6.21]%, P<0.05).PC-9 cells up-regulated the expressions of tight junction proteins of Bends cells under the treatment of AMD3100 (P<0.05). The number of PC-9 cells transmigrating the BBB in AMD3100 treatment group was significantly lower than that of CON group (43±2 vs 81±2,P<0.05). Conclusion: AMD3100 can reduce the ability of PC-9 cells destroying the tight junction of the BBB model established in vitro by Bends cells.
2020, 27(5):534-540.
DOI: 10.3872/j.issn.1007-385X.2020.05.010
Abstract:
Objective: To investigate the effects of exosome originated from bone marrow mesenchymal stem cell (BMSCs) on proliferation,migration and invasion of prostate cancer PC-3 cell and its mechanism. Methods: qPCR was used to detect the expression level of miR-21-5p in prostate cancer cell lines. The morphology of exosomes isolated from BMSCs was observed with an electron microscope.Western blotting was used to detect the expressions of exosome surface markers and the epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Vimentin). Dual luciferase reporter gene experiment was used to detect the targeted regulation relationship between miR-21-5p and PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2). PC-3 cells were co-cultured with 10 μl BMSCs exosomes suspension (Exo group), transfected with sh-PHLPP2 or antagomiR, then CCK-8 and Transwell experiments were used to detect changes in proliferation, migration and invasion of PC-3 cell. Results: miR-21-5p was highly expressed in prostate cancer PC-3 cell line. The exosomes in the supernatant of BMSCs culture fluid were successfully isolated, and the typical vesicle-like structures of exosomes were observed under transmission electron microscope. Exosomes expressed specific proteins such as CD9, CD63 and CD81. In the Exo group, the proliferation, invasion, migration, as well as the expressions of N-cadherin, Vimentin and miR-21-5p in PC-3 cells were significantly higher than those in the control group (all P<0.05). PHLPP2 is a target gene of miR-21-5p. Compared with the control group, the expression of PHLPP2 in PC-3 cells of Exo group and sh-PHLPP2 group was significantly reduced (0.66±0.09, 0.42±0.05 vs 1.09±0.08, all P<0.01); cell viability, invasion and migration were significantly improved (all P<0.01); and E-cadherin expression level was significantly reduced while N-cadherin and Vimentin expressions were significantly increased (both P<0.05). Conclusion: miR-21-5p is highly expressed in prostate cancer PC-3 cell line. BMSC exosome miR-21-5p can increase the proliferation, migration and invasion ability of PC-3 cells through targeted down-regulation of PHLPP2.
Objective: To investigate the effects of exosome originated from bone marrow mesenchymal stem cell (BMSCs) on proliferation,migration and invasion of prostate cancer PC-3 cell and its mechanism. Methods: qPCR was used to detect the expression level of miR-21-5p in prostate cancer cell lines. The morphology of exosomes isolated from BMSCs was observed with an electron microscope.Western blotting was used to detect the expressions of exosome surface markers and the epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Vimentin). Dual luciferase reporter gene experiment was used to detect the targeted regulation relationship between miR-21-5p and PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2). PC-3 cells were co-cultured with 10 μl BMSCs exosomes suspension (Exo group), transfected with sh-PHLPP2 or antagomiR, then CCK-8 and Transwell experiments were used to detect changes in proliferation, migration and invasion of PC-3 cell. Results: miR-21-5p was highly expressed in prostate cancer PC-3 cell line. The exosomes in the supernatant of BMSCs culture fluid were successfully isolated, and the typical vesicle-like structures of exosomes were observed under transmission electron microscope. Exosomes expressed specific proteins such as CD9, CD63 and CD81. In the Exo group, the proliferation, invasion, migration, as well as the expressions of N-cadherin, Vimentin and miR-21-5p in PC-3 cells were significantly higher than those in the control group (all P<0.05). PHLPP2 is a target gene of miR-21-5p. Compared with the control group, the expression of PHLPP2 in PC-3 cells of Exo group and sh-PHLPP2 group was significantly reduced (0.66±0.09, 0.42±0.05 vs 1.09±0.08, all P<0.01); cell viability, invasion and migration were significantly improved (all P<0.01); and E-cadherin expression level was significantly reduced while N-cadherin and Vimentin expressions were significantly increased (both P<0.05). Conclusion: miR-21-5p is highly expressed in prostate cancer PC-3 cell line. BMSC exosome miR-21-5p can increase the proliferation, migration and invasion ability of PC-3 cells through targeted down-regulation of PHLPP2.
2020, 27(5):541-546.
DOI: 10.3872/j.issn.1007-385X.2020.05.011
Abstract:
Objective: To investigate the expression and clinical significance of CEA mRNA in peritoneal lavage fluid for patients with gastric cancer after radical surgery. Methods: The clinical data of 139 gastric cancer patients, who underwent peritoneal lavage CEA mRNA detection after radical resection in the Comprehensive Cancer Centre of Drum Tower Hospital from January 2013 to December 2017 were retrospectively analyzed. Routine post-operative follow-up was conducted in all patients. The expression of CEA mRNA in peritoneal lavage fluid after radical resection of 139 gastric cancer patients was detected by RT-PCR. Chi-square test analysis was used to study the relationship between the expression of CEA mRNA in peritoneal lavage fluid and basic clinical features, histopathological data, hematological indicators and the recurrence pattern of GC patients. Logistic univariate and multivariate regression analyses were used to screen the influential factors affecting CEA mRNA expression. Results: CEA mRNA was positive in 44 (31.7%) of 139 patients. Analysis showed that there was no significant correlation between CEA mRNA expression and sex, age, pathological grade,Lauren type, HER2, EGFR, VEGFR and Ki67 (all P>0.05), but there was significant correlation between CEA mRNA expression and pathological type, vascular invasion, local invasion depth, lymph node metastasis and clinical AJCC stage (all P<0.05). The peritoneal recurrence rate of patients with positive CEA mRNA expression was significantly higher than that of patients with negative expression (P=0.012). Logistic univariate regression analysis showed that signet ring cell carcinoma (P=0.04, HR=2.810，95% CI: 1.050-7.520), T stage (P=0.016，HR=6.329, 95% CI: 1.417-28.264), N stage (P=0.022，HR=3.068，95% CI: 1.172-8.027), AJCC stage (P=0.016，HR=3.971, 95% CI: 1.295-12.173), nerve invasion (P=0.002, HR=6.738, 95% CI: 1.995-22.757) and vascular invasion (P<0.001, HR=16.36, 95% CI: 3.85-69.512) were risk factors for positive CEA mRNA expression in peritoneal lavage fluid of patients with gastric cancer. Logistic multivariate regression analysis showed that vascular invasion (P<0.001, HR=21.314，95% CI: 4.21-107.907) was an independent risk factor for positive CEA expression in peritoneal lavage fluid of gastric cancer patients. Conclusion: Gastric cancer patients with positive CEA mRNA in peritoneal lavage fluid have higher risk of peritoneal recurrence or metastasis and poorer prognosis.So, more aggressive anti-tumor treatments including local abdominal cavity treatment should be considered.
Objective: To investigate the expression and clinical significance of CEA mRNA in peritoneal lavage fluid for patients with gastric cancer after radical surgery. Methods: The clinical data of 139 gastric cancer patients, who underwent peritoneal lavage CEA mRNA detection after radical resection in the Comprehensive Cancer Centre of Drum Tower Hospital from January 2013 to December 2017 were retrospectively analyzed. Routine post-operative follow-up was conducted in all patients. The expression of CEA mRNA in peritoneal lavage fluid after radical resection of 139 gastric cancer patients was detected by RT-PCR. Chi-square test analysis was used to study the relationship between the expression of CEA mRNA in peritoneal lavage fluid and basic clinical features, histopathological data, hematological indicators and the recurrence pattern of GC patients. Logistic univariate and multivariate regression analyses were used to screen the influential factors affecting CEA mRNA expression. Results: CEA mRNA was positive in 44 (31.7%) of 139 patients. Analysis showed that there was no significant correlation between CEA mRNA expression and sex, age, pathological grade,Lauren type, HER2, EGFR, VEGFR and Ki67 (all P>0.05), but there was significant correlation between CEA mRNA expression and pathological type, vascular invasion, local invasion depth, lymph node metastasis and clinical AJCC stage (all P<0.05). The peritoneal recurrence rate of patients with positive CEA mRNA expression was significantly higher than that of patients with negative expression (P=0.012). Logistic univariate regression analysis showed that signet ring cell carcinoma (P=0.04, HR=2.810，95% CI: 1.050-7.520), T stage (P=0.016，HR=6.329, 95% CI: 1.417-28.264), N stage (P=0.022，HR=3.068，95% CI: 1.172-8.027), AJCC stage (P=0.016，HR=3.971, 95% CI: 1.295-12.173), nerve invasion (P=0.002, HR=6.738, 95% CI: 1.995-22.757) and vascular invasion (P<0.001, HR=16.36, 95% CI: 3.85-69.512) were risk factors for positive CEA mRNA expression in peritoneal lavage fluid of patients with gastric cancer. Logistic multivariate regression analysis showed that vascular invasion (P<0.001, HR=21.314，95% CI: 4.21-107.907) was an independent risk factor for positive CEA expression in peritoneal lavage fluid of gastric cancer patients. Conclusion: Gastric cancer patients with positive CEA mRNA in peritoneal lavage fluid have higher risk of peritoneal recurrence or metastasis and poorer prognosis.So, more aggressive anti-tumor treatments including local abdominal cavity treatment should be considered.
2020, 27(5):547-551.
DOI: 10.3872/j.issn.1007-385X.2020.05.012
Abstract:
Objective: To investigate the value of pre-treatment kisspeptin (KISS-1) expression for diagnosis and prognosis prediction of pancreatic cancer. Methods: The clinical data of 90 patients with pancreatic cancer (pancreatic cancer group) in Cancer Hospital of Hubei Province from April 2015 to December 2018 were retrospectively analyzed; in addition, 40 patients with benign pancreatic lesions were selected as the benign pancreatic lesion group and 30 healthy people were chosen as control group. The serum levels of KISS-1 and CA19-9 in each group were detected by ELISA. The diagnostic efficacies of CA19-9 and KISS-1 in pancreatic cancer and their relationship with the prognosis of pancreatic cancer were analyzed. Results: The serum KISS-1 level in the pancreatic cancer group was significantly higher than that in the benign pancreatic lesion group and the control group (both P<0.01); the area under the curve (AUC) of serum KISS-1, CA19-9 and their combination for pancreatic cancer detection was 0.757 (95% CI: 0.684-0.831,P=0.000), 0.900 (95% CI: 0.854-0.946, P=0.000), and 0.906 (95% CI: 0.861-0.950, P=0.000), respectively. The AUC value of the combined detection was statistically different from that of KISS-1 (Z=3.124, P=0.024), and the AUC value of CA19-9 was also statistically differently from KISS-1 (Z=3.253, P=0.025). Correlation analysis showed that there was a significant negative correlation between KISS-1 and CA19-9 (r=-0.358, P=0.002). The results of survival curve analysis showed that the survival time of patients with serum KISS-1≥73.6 pg/ml was significantly better than that of patients with KISS-1<73.6 pg/ml ( χ 2=4.520, P=0.036);KISS-1<73.6 pg/ml was independently related to the patient's prognosis with an OR of 2.37 (1.08-4.75). Conclusion: Serum KISS-1 is helpful for the early diagnosis of pancreatic cancer, and the combined detection of KISS-1 and CAI9-9 can improve the sensitivity and specificity of pancreatic cancer diagnosis, and also is beneficial for prognosis evaluation.
Objective: To investigate the value of pre-treatment kisspeptin (KISS-1) expression for diagnosis and prognosis prediction of pancreatic cancer. Methods: The clinical data of 90 patients with pancreatic cancer (pancreatic cancer group) in Cancer Hospital of Hubei Province from April 2015 to December 2018 were retrospectively analyzed; in addition, 40 patients with benign pancreatic lesions were selected as the benign pancreatic lesion group and 30 healthy people were chosen as control group. The serum levels of KISS-1 and CA19-9 in each group were detected by ELISA. The diagnostic efficacies of CA19-9 and KISS-1 in pancreatic cancer and their relationship with the prognosis of pancreatic cancer were analyzed. Results: The serum KISS-1 level in the pancreatic cancer group was significantly higher than that in the benign pancreatic lesion group and the control group (both P<0.01); the area under the curve (AUC) of serum KISS-1, CA19-9 and their combination for pancreatic cancer detection was 0.757 (95% CI: 0.684-0.831,P=0.000), 0.900 (95% CI: 0.854-0.946, P=0.000), and 0.906 (95% CI: 0.861-0.950, P=0.000), respectively. The AUC value of the combined detection was statistically different from that of KISS-1 (Z=3.124, P=0.024), and the AUC value of CA19-9 was also statistically differently from KISS-1 (Z=3.253, P=0.025). Correlation analysis showed that there was a significant negative correlation between KISS-1 and CA19-9 (r=-0.358, P=0.002). The results of survival curve analysis showed that the survival time of patients with serum KISS-1≥73.6 pg/ml was significantly better than that of patients with KISS-1<73.6 pg/ml ( χ 2=4.520, P=0.036);KISS-1<73.6 pg/ml was independently related to the patient's prognosis with an OR of 2.37 (1.08-4.75). Conclusion: Serum KISS-1 is helpful for the early diagnosis of pancreatic cancer, and the combined detection of KISS-1 and CAI9-9 can improve the sensitivity and specificity of pancreatic cancer diagnosis, and also is beneficial for prognosis evaluation.
2020, 27(5):552-558.
DOI: 10.3872/j.issn.1007-385X.2020.05.013
Abstract:
Objective: To explore the effect of lncRNA HOTAIR/miR-519d-3p/cyclin D1 (CCND1) axis on the proliferation and metastasis of breast cancer cells and its underlying mechanism. Methods: A total of 50 pairs of breast cancer tissues and corresponding para-cancer tissues resected from breast cancer patients in the Department of Breast Surgery, the Third Hospital of Nanchang from March 2017 to February 2019 were collected for this study. The expression level of HOTAIR in breast cancer tissues and paired paracancer tissues was detected by qPCR, in addition, the expressions of HOTAIR and miR-519d-3p in normal breast epithelial cells and breast cancer cell lines were also detected. Breast cancer SKBR3 cells were divided into NC group (without any treatment), si-HOTAIR group, mir-519d-3p mimics group, miR-519d-3p mimic+pcHOTAIR group, miR-519d-3p mimic+pcCCND1 group, and si-HOTAIR+ pcCCND1 group. The proliferation ability of SKBR3 cells was detected by CCK-8. Invasion and migration of SKBR3 cells were detected by Transwell. The expression levels of E-cadherin, N-cadherin, Vimentin and CCND1 in SKBR3 cells were detected by Western blotting. The targeting relationship between HOTAIR and miR-519d-3p, miR-519d-3p and CCND1 was detected by Dualluciferase reporter gene system. Results: HOTAIR was highly expressed in breast cancer tissues and cell lines, with the highest expression in SKBR3 cells. HOTAIR knockdown significantly inhibited the proliferation, invasion and migration of SKBR3 cells, as well as increased the expression level of E-cadherin and decreased the expression levels of N-cadherin and Vimentin. Dual-luciferase reporter gene assay showed that HOTAIR targetedly down-regulated the expression of miR-519d-3p, and miR-519d-3p targetedly downregulated the expression of CCND1. Further studies showed that knockout of HOTAIR inhibited the EMT, proliferation, invasion and migration of SKBR3 cells through enhancing the inhibitory effect of miR-519d-3p on CCND1 expression (all P<0.05). Conclusion:HOTAIR knockdown inhibits proliferation and metastasis of SKBR3 cells by regulating the axis of miR-519d-3p/CCND1.
Objective: To explore the effect of lncRNA HOTAIR/miR-519d-3p/cyclin D1 (CCND1) axis on the proliferation and metastasis of breast cancer cells and its underlying mechanism. Methods: A total of 50 pairs of breast cancer tissues and corresponding para-cancer tissues resected from breast cancer patients in the Department of Breast Surgery, the Third Hospital of Nanchang from March 2017 to February 2019 were collected for this study. The expression level of HOTAIR in breast cancer tissues and paired paracancer tissues was detected by qPCR, in addition, the expressions of HOTAIR and miR-519d-3p in normal breast epithelial cells and breast cancer cell lines were also detected. Breast cancer SKBR3 cells were divided into NC group (without any treatment), si-HOTAIR group, mir-519d-3p mimics group, miR-519d-3p mimic+pcHOTAIR group, miR-519d-3p mimic+pcCCND1 group, and si-HOTAIR+ pcCCND1 group. The proliferation ability of SKBR3 cells was detected by CCK-8. Invasion and migration of SKBR3 cells were detected by Transwell. The expression levels of E-cadherin, N-cadherin, Vimentin and CCND1 in SKBR3 cells were detected by Western blotting. The targeting relationship between HOTAIR and miR-519d-3p, miR-519d-3p and CCND1 was detected by Dualluciferase reporter gene system. Results: HOTAIR was highly expressed in breast cancer tissues and cell lines, with the highest expression in SKBR3 cells. HOTAIR knockdown significantly inhibited the proliferation, invasion and migration of SKBR3 cells, as well as increased the expression level of E-cadherin and decreased the expression levels of N-cadherin and Vimentin. Dual-luciferase reporter gene assay showed that HOTAIR targetedly down-regulated the expression of miR-519d-3p, and miR-519d-3p targetedly downregulated the expression of CCND1. Further studies showed that knockout of HOTAIR inhibited the EMT, proliferation, invasion and migration of SKBR3 cells through enhancing the inhibitory effect of miR-519d-3p on CCND1 expression (all P<0.05). Conclusion:HOTAIR knockdown inhibits proliferation and metastasis of SKBR3 cells by regulating the axis of miR-519d-3p/CCND1.
2020, 27(5):559-565.
DOI: 10.3872/j.issn.1007-385X.2020.05.014
Abstract:
针对癌症的传统治疗手段主要有手术治疗、化疗、放疗等。这些方法虽然能在一定程度上控制肿瘤生长，但也存在一定的技术局限性。溶瘤病毒疗法作为一种新型的肿瘤细胞生物疗法，为恶性肿瘤的治疗带来了新的发展希望。溶瘤病毒能够在不影响正常细胞的情况下，发挥较强的肿瘤抑制和杀伤作用，同时通过免疫诱导促使机体产生抗肿瘤免疫反应，进一步提高对肿瘤细胞的杀伤效果。然而，由于病毒自身存在较强的免疫原性，静脉注射后会引发机体产生不同程度的免疫应答，并且溶瘤病毒的肿瘤靶向性和单独治疗能力有限，使得其最终的肿瘤治疗效果并不理想。研究者通过设计并构建不同类型的载体来装载病毒，以封闭其固有的免疫原性，延长其血液循环时间的同时，进一步提高其对恶性肿瘤的靶向性，并在此基础上将溶瘤病毒与其他肿瘤治疗手段结合，进而增强溶瘤病毒的肿瘤治疗效果。本文将重点围绕如何有效构建溶瘤病毒载体及联合其他肿瘤治疗手段以提高溶瘤病毒的肿瘤治疗效果，对近期相关研究进展进行综述介绍。
针对癌症的传统治疗手段主要有手术治疗、化疗、放疗等。这些方法虽然能在一定程度上控制肿瘤生长，但也存在一定的技术局限性。溶瘤病毒疗法作为一种新型的肿瘤细胞生物疗法，为恶性肿瘤的治疗带来了新的发展希望。溶瘤病毒能够在不影响正常细胞的情况下，发挥较强的肿瘤抑制和杀伤作用，同时通过免疫诱导促使机体产生抗肿瘤免疫反应，进一步提高对肿瘤细胞的杀伤效果。然而，由于病毒自身存在较强的免疫原性，静脉注射后会引发机体产生不同程度的免疫应答，并且溶瘤病毒的肿瘤靶向性和单独治疗能力有限，使得其最终的肿瘤治疗效果并不理想。研究者通过设计并构建不同类型的载体来装载病毒，以封闭其固有的免疫原性，延长其血液循环时间的同时，进一步提高其对恶性肿瘤的靶向性，并在此基础上将溶瘤病毒与其他肿瘤治疗手段结合，进而增强溶瘤病毒的肿瘤治疗效果。本文将重点围绕如何有效构建溶瘤病毒载体及联合其他肿瘤治疗手段以提高溶瘤病毒的肿瘤治疗效果，对近期相关研究进展进行综述介绍。
2020, 27(5):566-570.
DOI: 10.3872/j.issn.1007-385X.2020.05.015
Abstract:
以PD-1/PD-L1 轴为靶点的免疫检查点阻断治疗策略已经应用于临床上多种肿瘤的治疗。PD-L1 作为表达于肿瘤细胞中的重要免疫调控靶点，可以应用单克隆抗体阻断其介导的免疫抑制作用，从而恢复T细胞对肿瘤细胞的识别和杀伤。但是，PD-L1 的表达受多种因素调控，包括基因组水平、翻译后修饰过程以及翻译后CMTM4/6 介导的内含体循环调控等。本文就PD-L1 蛋白表达的受调控过程及其在胶质瘤免疫治疗中作用的研究进展作一综述。
以PD-1/PD-L1 轴为靶点的免疫检查点阻断治疗策略已经应用于临床上多种肿瘤的治疗。PD-L1 作为表达于肿瘤细胞中的重要免疫调控靶点，可以应用单克隆抗体阻断其介导的免疫抑制作用，从而恢复T细胞对肿瘤细胞的识别和杀伤。但是，PD-L1 的表达受多种因素调控，包括基因组水平、翻译后修饰过程以及翻译后CMTM4/6 介导的内含体循环调控等。本文就PD-L1 蛋白表达的受调控过程及其在胶质瘤免疫治疗中作用的研究进展作一综述。
2020, 27(5):571-576.
DOI: 10.3872/j.issn.1007-385X.2020.05.016
Abstract:
晚期结直肠癌患者很难从手术和放化疗等传统治疗中获益，从结直肠癌发生发展的分子机制入手探索新的治疗靶点和方法意义重大。叉头框M1(forkhead box M1，FOXM1)转录因子的异常表达与结直肠癌的发生进展密切相关，异常表达的FOXM1 可通过促进上皮-间充质转化、肿瘤血管生成、调节肿瘤干细胞特性、信号转导通路等影响结直肠癌细胞的增殖、侵袭、转移和放化疗抵抗。本文主要就FOXM1 在结直肠癌中的作用及其作用机制的最新研究进展作一综述，以期为临床结直肠癌的治疗提供新的理论依据和治疗靶标。
晚期结直肠癌患者很难从手术和放化疗等传统治疗中获益，从结直肠癌发生发展的分子机制入手探索新的治疗靶点和方法意义重大。叉头框M1(forkhead box M1，FOXM1)转录因子的异常表达与结直肠癌的发生进展密切相关，异常表达的FOXM1 可通过促进上皮-间充质转化、肿瘤血管生成、调节肿瘤干细胞特性、信号转导通路等影响结直肠癌细胞的增殖、侵袭、转移和放化疗抵抗。本文主要就FOXM1 在结直肠癌中的作用及其作用机制的最新研究进展作一综述，以期为临床结直肠癌的治疗提供新的理论依据和治疗靶标。
2020, 27(5):577-581.
DOI: 10.3872/j.issn.1007-385X.2020.05.017
Abstract:
宫颈癌是我国女性常见的恶性肿瘤，其传统治疗方式仍存在较多的毒副作用，在寻求突破治疗宫颈癌的新途径中，程序性死亡受体（programmed cell death-1，PD-1）和程序性死亡配体（programmed cell death-ligand 1，PD-L1）是近年来研究较多的抑制性免疫检查点，其与多种恶性肿瘤的发生、发展和转移有不可分割的联系。PD-1/PD-L1 抑制剂在治疗宫颈癌方面，其总体缓解率为14%～27%，当其联合传统化疗可以更多地提高总体缓解率，目前已有多项相关研究正在进行中。本文对PD-1/PD-L1 的生物学特性及其抗体在宫颈癌治疗中的应用进展作一综述。
宫颈癌是我国女性常见的恶性肿瘤，其传统治疗方式仍存在较多的毒副作用，在寻求突破治疗宫颈癌的新途径中，程序性死亡受体（programmed cell death-1，PD-1）和程序性死亡配体（programmed cell death-ligand 1，PD-L1）是近年来研究较多的抑制性免疫检查点，其与多种恶性肿瘤的发生、发展和转移有不可分割的联系。PD-1/PD-L1 抑制剂在治疗宫颈癌方面，其总体缓解率为14%～27%，当其联合传统化疗可以更多地提高总体缓解率，目前已有多项相关研究正在进行中。本文对PD-1/PD-L1 的生物学特性及其抗体在宫颈癌治疗中的应用进展作一综述。
2020, 27(5):582-588.
DOI: 10.3872/j.issn.1007-385X.2020.05.018
Abstract:
细胞焦亡是一种以促炎为特点的细胞程序性死亡方式，其生物学特征为依赖于半胱氨酸天冬蛋白酶（caspases）家族蛋白切割gasdermin 家族蛋白，使活化的gasdermin 家族蛋白在质膜上形成离子穿孔，导致细胞肿胀裂解。目前已知的细胞焦亡信号途径包括gasdermin-D（GSDMD）介导的经典途径和非经典途径，以及gasdermin-E（GSDME）介导的化疗药物等处理后的细胞焦亡途径。越来越多的研究显示，细胞焦亡与肿瘤细胞死亡及相关正常组织细胞损伤密切相关，陆续有多种药物或者提取物被证实其抗肿瘤分子机制与焦亡相关，这为抗肿瘤治疗的研究提供了新的思路和方法。本文就细胞焦亡的分子机制与焦亡相关药物抗肿瘤治疗的研究进展进行综述。
细胞焦亡是一种以促炎为特点的细胞程序性死亡方式，其生物学特征为依赖于半胱氨酸天冬蛋白酶（caspases）家族蛋白切割gasdermin 家族蛋白，使活化的gasdermin 家族蛋白在质膜上形成离子穿孔，导致细胞肿胀裂解。目前已知的细胞焦亡信号途径包括gasdermin-D（GSDMD）介导的经典途径和非经典途径，以及gasdermin-E（GSDME）介导的化疗药物等处理后的细胞焦亡途径。越来越多的研究显示，细胞焦亡与肿瘤细胞死亡及相关正常组织细胞损伤密切相关，陆续有多种药物或者提取物被证实其抗肿瘤分子机制与焦亡相关，这为抗肿瘤治疗的研究提供了新的思路和方法。本文就细胞焦亡的分子机制与焦亡相关药物抗肿瘤治疗的研究进展进行综述。
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- 《中国肿瘤生物治疗杂志》
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.