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Volume 25,Issue 7,2018 Table of Contents
2018, 25(7):663-668.
DOI: 10.3872/j.issn.1007-385X.2018.07.001
Abstract:
[Abstract] In recent years, therapy of immune checkpoint inhibitors have developed rapidly and made breakthrough, becoming the first-line treatment for many types of advanced cancer. However, due to its particular mode in activating the anti-tumor immune system,a variety of unconventional response patterns have emerged, such as delayed response and pseudoprogression, which have challenged the traditional response evaluation criteria and encouraged people to continuously explore new criteria for evaluating the unconventional response patterns under immunotherapy. This article mainly reviews the process of exploration, advanced research,as well as similarities and differencesamongvarious immune-related efficacy evaluation criteria, and finally prospects the current challenges and future trends.
[Abstract] In recent years, therapy of immune checkpoint inhibitors have developed rapidly and made breakthrough, becoming the first-line treatment for many types of advanced cancer. However, due to its particular mode in activating the anti-tumor immune system,a variety of unconventional response patterns have emerged, such as delayed response and pseudoprogression, which have challenged the traditional response evaluation criteria and encouraged people to continuously explore new criteria for evaluating the unconventional response patterns under immunotherapy. This article mainly reviews the process of exploration, advanced research,as well as similarities and differencesamongvarious immune-related efficacy evaluation criteria, and finally prospects the current challenges and future trends.
2018, 25(7):669-673.
DOI: 10.3872/j.issn.1007-385X.2018.07.002
Abstract:
[Abstract] Over the last few decades progress in the field of stem cell biology makes a new kind of 3-D human cells in vitro culture techniques available, which is termed organoids because of its space structure similar to organs. Organoids derived from tumor tissues largely retained the biological characteristics of tumor tissue in vivo, and both the advantages of low cost and easy operation make up the defects of the previous conventional cancer models. Organoids can also be used for translational medical research, formulating individual therapeutic schedules including drug sensitive tests, and combining with many kinds of technologies. This article focus on the application and prospects of organoids in tumor research.
[Abstract] Over the last few decades progress in the field of stem cell biology makes a new kind of 3-D human cells in vitro culture techniques available, which is termed organoids because of its space structure similar to organs. Organoids derived from tumor tissues largely retained the biological characteristics of tumor tissue in vivo, and both the advantages of low cost and easy operation make up the defects of the previous conventional cancer models. Organoids can also be used for translational medical research, formulating individual therapeutic schedules including drug sensitive tests, and combining with many kinds of technologies. This article focus on the application and prospects of organoids in tumor research.
WANG Xiaodong
,
HU Zhihao
,
ZHANG Wei
,
PANG Cui
,
DUAN Qiong
,
WANG Jinyan
,
LIU Wenchao
,
ZHANG Ju
2018, 25(7):674-679.
DOI: 10.3872/j.issn.1007-385X.2018.07.003
Abstract:
Objective: To investigate the effect of DAMP (damaged associated molecular pattern) on the inhibition of RAS-mutant A549 lung adenocarcinoma cells by CIK cells and its mechanism. Methods: Human peripheral blood mononuclear cells were isolated in vitro and CIK cells were cultured. A549 cells were treated with cisplatin (DDP) and doxorubicin (ADM) alone or in combination,and the morphology of A549 cells was observed under a microscope. The supernatant of A549 cells was co-cultured with CIK cells.Flow cytometry was used to detect the CIK cell immunophenotype after co-culture. MTT assay was used to detect the inhibition of A549 lung cancer cell proliferation induced by A549 cell supernatant. The concentration of chemotherapeutic drugs kills A549 cell supernatant CRT, ATP, HMGB1 content. Results: Low-level chemotherapeutic drugs showed more immunogenic death characteristics after killing A549 cells. The ratio of CD8+ and CD56+ in CIK cells was significantly higher than that in control CIK cells (P<0.05). The inhibition rate of CIK cells induced by A549 cells after injury on A549 lung adenocarcinoma cells was significantly higher than that of the same dose chemotherapy group [DDP group (31.34±1.51)% vs (5.97±1.74)%, ADM group (45.46±1.78)% vs (6.22±1.34)%, DDP+ADM group (45.78±1.14)% vs (11.94±3.11)%, all P<0.05], and low-mass chemotherapeutic agents killed C549 induced by A549 cell supernatant on A549 The inhibition rate of the cells was higher than that of the supernatant induced by the higher concentration of che-motherapeutic drugs (all P<0.05). The level of CRT, ATP, and HMGB1 in immunogenicity-related molecules in the supernatant of A549 cells was significantly increased by low-concentration chemotherapy drugs (all P<0.05). In the low-concentration group, the supernatant-induced inhibition of the proliferation of A549 lung adenocarcinoma cells increased with the increase of CRT, ATP, and HMGB1 levels. Conclusion: The combination of lower concentration of DDP and ADM alone or in combination could more easily induce the immunogenic death of A549 cells and release higher levels of DAMP molecules, which could promote the inhibitory effect of CIK on lung cancer A549 cells.
Objective: To investigate the effect of DAMP (damaged associated molecular pattern) on the inhibition of RAS-mutant A549 lung adenocarcinoma cells by CIK cells and its mechanism. Methods: Human peripheral blood mononuclear cells were isolated in vitro and CIK cells were cultured. A549 cells were treated with cisplatin (DDP) and doxorubicin (ADM) alone or in combination,and the morphology of A549 cells was observed under a microscope. The supernatant of A549 cells was co-cultured with CIK cells.Flow cytometry was used to detect the CIK cell immunophenotype after co-culture. MTT assay was used to detect the inhibition of A549 lung cancer cell proliferation induced by A549 cell supernatant. The concentration of chemotherapeutic drugs kills A549 cell supernatant CRT, ATP, HMGB1 content. Results: Low-level chemotherapeutic drugs showed more immunogenic death characteristics after killing A549 cells. The ratio of CD8+ and CD56+ in CIK cells was significantly higher than that in control CIK cells (P<0.05). The inhibition rate of CIK cells induced by A549 cells after injury on A549 lung adenocarcinoma cells was significantly higher than that of the same dose chemotherapy group [DDP group (31.34±1.51)% vs (5.97±1.74)%, ADM group (45.46±1.78)% vs (6.22±1.34)%, DDP+ADM group (45.78±1.14)% vs (11.94±3.11)%, all P<0.05], and low-mass chemotherapeutic agents killed C549 induced by A549 cell supernatant on A549 The inhibition rate of the cells was higher than that of the supernatant induced by the higher concentration of che-motherapeutic drugs (all P<0.05). The level of CRT, ATP, and HMGB1 in immunogenicity-related molecules in the supernatant of A549 cells was significantly increased by low-concentration chemotherapy drugs (all P<0.05). In the low-concentration group, the supernatant-induced inhibition of the proliferation of A549 lung adenocarcinoma cells increased with the increase of CRT, ATP, and HMGB1 levels. Conclusion: The combination of lower concentration of DDP and ADM alone or in combination could more easily induce the immunogenic death of A549 cells and release higher levels of DAMP molecules, which could promote the inhibitory effect of CIK on lung cancer A549 cells.
2018, 25(7):680-686.
DOI: 10.3872/j.issn.1007-385X.2018.07.004
Abstract:
Objective: To observe the effect of SHIP1 on NSCLC cell proliferation. Methods: The CDS region of human SHIP1 gene was obtained by inquiring NCBI Gene database and was inserted into the vector pTSB-CMV-MCS-SBP-3Flag-EGFP to construct SHIP1 over-expression plasmid, which was further used to construct SHIP1 overexpression lentivirus. SHIP1 over-expressed lentiviruses were used to transfect A549, SPCA-1 and PC-9 cell lines to construct SHIP1 overexpressed NSCLC cell line. Western blotting and qRT-PCR were used to determine the protein and mRNA expression of SHIP1. The MTT assay and Clone formation assay were used to examine the cell proliferation ability and clone formation ability of PC-9 cells overexpressed SHIP1; Western blotting was performed to examine the level of AP-1 proteins. Results: The sequencing result suggested that the SHIP1 eukaryotic over-expression plasmid was successfully constructed. A519, SPCA-1 and PC-9 cells with SHIP1 over-expression were observed to display uniform green fluorescence under fluorescent microscopy. Compared with negative control group, the mRNA and protein levels of SHIP1 were significantly increased in SHIP1 overexpressed cells (all P<0.01). The over-expression of SHIP1 suppressed the abilities of proliferation and clone formation in PC-9 cells (all P<0.01), and down-regulated the expression of p-c-Jun and FosB etc. Conclusion: The SHIP1 overexpressed NSCLC cell lines were successfully established, and the over-expression of SHIP1 suppressed the cell proliferation ability by inhibiting AP-1 proteins in NSCLC cell lines.
Objective: To observe the effect of SHIP1 on NSCLC cell proliferation. Methods: The CDS region of human SHIP1 gene was obtained by inquiring NCBI Gene database and was inserted into the vector pTSB-CMV-MCS-SBP-3Flag-EGFP to construct SHIP1 over-expression plasmid, which was further used to construct SHIP1 overexpression lentivirus. SHIP1 over-expressed lentiviruses were used to transfect A549, SPCA-1 and PC-9 cell lines to construct SHIP1 overexpressed NSCLC cell line. Western blotting and qRT-PCR were used to determine the protein and mRNA expression of SHIP1. The MTT assay and Clone formation assay were used to examine the cell proliferation ability and clone formation ability of PC-9 cells overexpressed SHIP1; Western blotting was performed to examine the level of AP-1 proteins. Results: The sequencing result suggested that the SHIP1 eukaryotic over-expression plasmid was successfully constructed. A519, SPCA-1 and PC-9 cells with SHIP1 over-expression were observed to display uniform green fluorescence under fluorescent microscopy. Compared with negative control group, the mRNA and protein levels of SHIP1 were significantly increased in SHIP1 overexpressed cells (all P<0.01). The over-expression of SHIP1 suppressed the abilities of proliferation and clone formation in PC-9 cells (all P<0.01), and down-regulated the expression of p-c-Jun and FosB etc. Conclusion: The SHIP1 overexpressed NSCLC cell lines were successfully established, and the over-expression of SHIP1 suppressed the cell proliferation ability by inhibiting AP-1 proteins in NSCLC cell lines.
2018, 25(7):687-692.
DOI: 10.3872/j.issn.1007-385X.2018.07.005
Abstract:
Objective: To investigate the effects of costunolide (Cos) on the proliferation, apoptosis, migration andinvasion of cholangiocarcinoma RBE cells, and explore its potential mechanism. Methods: The CCK-8, flow cytometry, Annexin V-FITC/PI double staining,Transwell assays were used to examine the influence of Cos on proliferation, cell cycle, apoptosis, migration and invasion of RBE cells after treated with gradient concentrations of Cos. The expressions of MMP2 and MMP9 were detected by qRT-PCR, and the expression of PI3K/AKT-associated signal proteins was detected by Western blotting. Results: Cosdose-dependently inhibited proliferation activity of RBE cells(P<0.05 or P<0.01), arrested cell cycle at S and G2/M phases and induced RBE cell apoptosis(P<0.01). Transwell and qRT-PCR results demonstrated that Cos impeded RBE cell migration, invasion, and reduced the transcription of MMP2 and MMP9. Cos inhibited the expressionofp-AKT, Bcl-2, MMP2 and MMP9, the level of Bax. Conclusion: Cos restrained the proliferation,migration and invasion of RBE cells by suppressing PI3K/AKTpathway.
Objective: To investigate the effects of costunolide (Cos) on the proliferation, apoptosis, migration andinvasion of cholangiocarcinoma RBE cells, and explore its potential mechanism. Methods: The CCK-8, flow cytometry, Annexin V-FITC/PI double staining,Transwell assays were used to examine the influence of Cos on proliferation, cell cycle, apoptosis, migration and invasion of RBE cells after treated with gradient concentrations of Cos. The expressions of MMP2 and MMP9 were detected by qRT-PCR, and the expression of PI3K/AKT-associated signal proteins was detected by Western blotting. Results: Cosdose-dependently inhibited proliferation activity of RBE cells(P<0.05 or P<0.01), arrested cell cycle at S and G2/M phases and induced RBE cell apoptosis(P<0.01). Transwell and qRT-PCR results demonstrated that Cos impeded RBE cell migration, invasion, and reduced the transcription of MMP2 and MMP9. Cos inhibited the expressionofp-AKT, Bcl-2, MMP2 and MMP9, the level of Bax. Conclusion: Cos restrained the proliferation,migration and invasion of RBE cells by suppressing PI3K/AKTpathway.
6 Preliminary investigation of TIM-3 ligand galectin-9 inducing apoptosis of NK/T cell lymphoma cells
2018, 25(7):693-697.
DOI: 10.3872/j.issn.1007-385X.2018.07.006
Abstract:
Objective: To identify the expression pattern of TIM-3 in natural killer/T-cell lymphoma (NK/TCL) cell lines, and to investigate the effect and mechanism of its ligand galectin-9 (GAL-9) inducing apoptosis of NK/TCL cell lines. Methods: Expression of TIM-3 in NK cell of peripheral blood from healthy donors and NK/TCL cell lines (SNK-1、SNK-6、SNT-8) was detected by Western blotting. After being treated with rhGAL-9 at various concentrations for 24h, the cell proliferation ability was analyzed with CCK-8 assay.Apoptosis ratio of the cells was determined by flow cytometry. Expressions of caspase-3, PARP and their cleavages were detected by Western blotting; moreover, phosphorylation levels of proteins in MAPK signaling pathway were also detected by Western blotting.Results: The expression of TIM-3 in SNK-1, SNK-6 and SNT-8 cell lines was significantly higher than that of NK cells from healthy donors (P<0.05). CCK-8 result showed that rhGAL-9 obviously inhibited the proliferation of NK/TCL cell lines in a concentration dependent manner. Flow cytometry showed that rhGAL-9 induced the apoptosis of NK/TCL cells; andWestern blotting proved that the expression of cleaved caspase-3, cleaved-PARP, and p-JNK in MAPK signaling pathway were significantly elevated. Conclusion: TIM-3 was over-expressed in NK/TCL cell lines, and its ligand galectin-9 induced cell apoptosis probably through the activation of JNK kinase pathways.
Objective: To identify the expression pattern of TIM-3 in natural killer/T-cell lymphoma (NK/TCL) cell lines, and to investigate the effect and mechanism of its ligand galectin-9 (GAL-9) inducing apoptosis of NK/TCL cell lines. Methods: Expression of TIM-3 in NK cell of peripheral blood from healthy donors and NK/TCL cell lines (SNK-1、SNK-6、SNT-8) was detected by Western blotting. After being treated with rhGAL-9 at various concentrations for 24h, the cell proliferation ability was analyzed with CCK-8 assay.Apoptosis ratio of the cells was determined by flow cytometry. Expressions of caspase-3, PARP and their cleavages were detected by Western blotting; moreover, phosphorylation levels of proteins in MAPK signaling pathway were also detected by Western blotting.Results: The expression of TIM-3 in SNK-1, SNK-6 and SNT-8 cell lines was significantly higher than that of NK cells from healthy donors (P<0.05). CCK-8 result showed that rhGAL-9 obviously inhibited the proliferation of NK/TCL cell lines in a concentration dependent manner. Flow cytometry showed that rhGAL-9 induced the apoptosis of NK/TCL cells; andWestern blotting proved that the expression of cleaved caspase-3, cleaved-PARP, and p-JNK in MAPK signaling pathway were significantly elevated. Conclusion: TIM-3 was over-expressed in NK/TCL cell lines, and its ligand galectin-9 induced cell apoptosis probably through the activation of JNK kinase pathways.
2018, 25(7):698-703.
DOI: 10.3872/j.issn.1007-385X.2018.07.007
Abstract:
Objective: To study the effects of microRNA-1180-5p (miR-1180-5p) on malignant biological behaviors of prostate cancer VCAP and LNCaP cells and the possible mechanisms. Methods: dsControl (dsControl group) and miR-1180-5p (miR-1180-5p group)were constructed and then transfected into two prostate cancer cell lines VCAP and LNCaP. qPCR andWestern blotting were used to analyze the changes in mRNA and protein expressions of CDKN1A, Cyclin D1 and CDK6 after transfection. Cell cycle distribution, proliferation activity, clone formation capacity, cell migration and invasion ability were detected by flow cytometry, MTT assay, colony culture assay and Transwell assay, respectively. Results: qPCR results showed that compared with dsControl, CDKN1A mRNA levels in VCAP and LNCaP cells transfected with miR-1180-5p were up-regulated significantly, while the mRNA expressions of Cyclin D1 and CDK6 were significantly down-regulated (all P<0.01). Western blotting result was consistent with that of qPCR. The percentage of cells in G0/G1 phase was increased after transfection of miR-1180-5p (P<0.05), but the proportion of cells in S phase and G2/M phase was decreased and the cell cycle was arrested at G0/G1 phase (P<0.05). The proliferation activity of the two prostate cancer cells was significantly lower than that of the dsControl group after miR-1180-5p transfection (P<0.05), and the number of colonies in the miR-1180-5p group was significantly lower than that in the dsControl group (P<0.01). In the meanwhile, the cell migration and invasion ability in miR-1180-5p group was decreased (P<0.01). Conclusion: miR-1180-5p can significantly activate CDKN1A gene expression in prostate cancer cells and further inhibit the proliferation, migration and invasion of prostate cancer cells.
Objective: To study the effects of microRNA-1180-5p (miR-1180-5p) on malignant biological behaviors of prostate cancer VCAP and LNCaP cells and the possible mechanisms. Methods: dsControl (dsControl group) and miR-1180-5p (miR-1180-5p group)were constructed and then transfected into two prostate cancer cell lines VCAP and LNCaP. qPCR andWestern blotting were used to analyze the changes in mRNA and protein expressions of CDKN1A, Cyclin D1 and CDK6 after transfection. Cell cycle distribution, proliferation activity, clone formation capacity, cell migration and invasion ability were detected by flow cytometry, MTT assay, colony culture assay and Transwell assay, respectively. Results: qPCR results showed that compared with dsControl, CDKN1A mRNA levels in VCAP and LNCaP cells transfected with miR-1180-5p were up-regulated significantly, while the mRNA expressions of Cyclin D1 and CDK6 were significantly down-regulated (all P<0.01). Western blotting result was consistent with that of qPCR. The percentage of cells in G0/G1 phase was increased after transfection of miR-1180-5p (P<0.05), but the proportion of cells in S phase and G2/M phase was decreased and the cell cycle was arrested at G0/G1 phase (P<0.05). The proliferation activity of the two prostate cancer cells was significantly lower than that of the dsControl group after miR-1180-5p transfection (P<0.05), and the number of colonies in the miR-1180-5p group was significantly lower than that in the dsControl group (P<0.01). In the meanwhile, the cell migration and invasion ability in miR-1180-5p group was decreased (P<0.01). Conclusion: miR-1180-5p can significantly activate CDKN1A gene expression in prostate cancer cells and further inhibit the proliferation, migration and invasion of prostate cancer cells.
2018, 25(7):704-710.
DOI: 10.3872/j.issn.1007-385X.2018.07.008
Abstract:
Objective: To explore the effects of miR-149-3p on the proliferation, apoptosis, invasion and migration of cervical cancer HeLa cells and the possible mechanisms. Methods: HeLa cells were randomly divided into five groups, including untransfected (HeLa)group, mimic-scramble group (the negative control of miR-149 mimic), miR-149 mimic group, FOXP3 over-expression (pc-FOXP3)group, and co-transfection (mimic+pc-FOXP3) group. The targeted relationship of miR-149-3p and FOXP3 was verified by luciferase assay. The expressions of miR-149-3p and FOXP3 mRNA were tested by quantitative real-time reverse transcription PCR (qRT-PCR).The protein levels of FOXP3 were measured by Western blotting. The proliferation was detected by CCK-8; the apoptosis was tested by flow cytometry, the cell invasion was measured by transwell invasion assay and cell migration was detected by scratch assay. Results:The luciferase assay showed that miR-149-3p could target combine with FOXP3. Compared with untransfected group, the expression of miR-149-3p was increased while mRNA level of FOXP3 was decreased in miR-149 mimic group (all P<0.01). Moreover, the protein level of FOXP3 in miR-149 mimic group was lower than that in untransfected group (P<0.01), while the protein level of FOXP3 in pc-FOXP3 group was higher than that in untransfected group (P<0.01); Compared with pc-FOXP3 group, the protein levels of FOXP3 in mimic+pc-FOXP3 group were reduced (P<0.01). The proliferation in miR-149 mimic group was lower than that in untransfected group (P<0.01), while the proliferation in pc-FOXP3 was higher than that in untransfected group (P<0.01); compared with pc-FOXP3 group,the proliferation in mimic+pc-FOXP3 group was decreased (P<0.01). The apoptosis rate of HeLa cells in miR-149 mimic group was higher than that in untransfected group (P<0.01), while the apoptosis rate in pc-FOXP3 was lower than that in untransfected group (P<0.01); compared with pc-FOXP3 group, the apoptosis in mimic+pc-FOXP3 group was elevated (P<0.01). The number of invasive cells per field and wound healing rate in miR-149 mimic group was lower than those in untransfeccted group (P<0.01) while the invasive cells and wound healing rate in pc-FOXP3 group was higher than those in untransfeceted group (P<0.01); compared with pc-FOXP3 group, the number of invasive cells per field and wound healing rate in mimic+pc-FOXP3 group was reduced (P<0.01). Conclusion:miR-149-3p inhibits proliferation, invasion and migration and promotes apoptosis of cervical cancer HeLa cells via targeting FOXP3.
Objective: To explore the effects of miR-149-3p on the proliferation, apoptosis, invasion and migration of cervical cancer HeLa cells and the possible mechanisms. Methods: HeLa cells were randomly divided into five groups, including untransfected (HeLa)group, mimic-scramble group (the negative control of miR-149 mimic), miR-149 mimic group, FOXP3 over-expression (pc-FOXP3)group, and co-transfection (mimic+pc-FOXP3) group. The targeted relationship of miR-149-3p and FOXP3 was verified by luciferase assay. The expressions of miR-149-3p and FOXP3 mRNA were tested by quantitative real-time reverse transcription PCR (qRT-PCR).The protein levels of FOXP3 were measured by Western blotting. The proliferation was detected by CCK-8; the apoptosis was tested by flow cytometry, the cell invasion was measured by transwell invasion assay and cell migration was detected by scratch assay. Results:The luciferase assay showed that miR-149-3p could target combine with FOXP3. Compared with untransfected group, the expression of miR-149-3p was increased while mRNA level of FOXP3 was decreased in miR-149 mimic group (all P<0.01). Moreover, the protein level of FOXP3 in miR-149 mimic group was lower than that in untransfected group (P<0.01), while the protein level of FOXP3 in pc-FOXP3 group was higher than that in untransfected group (P<0.01); Compared with pc-FOXP3 group, the protein levels of FOXP3 in mimic+pc-FOXP3 group were reduced (P<0.01). The proliferation in miR-149 mimic group was lower than that in untransfected group (P<0.01), while the proliferation in pc-FOXP3 was higher than that in untransfected group (P<0.01); compared with pc-FOXP3 group,the proliferation in mimic+pc-FOXP3 group was decreased (P<0.01). The apoptosis rate of HeLa cells in miR-149 mimic group was higher than that in untransfected group (P<0.01), while the apoptosis rate in pc-FOXP3 was lower than that in untransfected group (P<0.01); compared with pc-FOXP3 group, the apoptosis in mimic+pc-FOXP3 group was elevated (P<0.01). The number of invasive cells per field and wound healing rate in miR-149 mimic group was lower than those in untransfeccted group (P<0.01) while the invasive cells and wound healing rate in pc-FOXP3 group was higher than those in untransfeceted group (P<0.01); compared with pc-FOXP3 group, the number of invasive cells per field and wound healing rate in mimic+pc-FOXP3 group was reduced (P<0.01). Conclusion:miR-149-3p inhibits proliferation, invasion and migration and promotes apoptosis of cervical cancer HeLa cells via targeting FOXP3.
2018, 25(7):711-715.
DOI: 10.3872/j.issn.1007-385X.2018.07.009
Abstract:
Objective: To investigate the influence of inhibiting expression of polyamine-modulated factor (PMF-1) on the antitumor effect of glucocorticoid dexamethasone (DEX) in human cervical cancer Caski cells. Methods: siRNAs which target human PMF-1 gene were designed and synthesized, and their effect on the expression of PMF-1 in Caski cells was evaluated by Western blotting. The PMF-1 down-regulated and control Caski cells were treated with DEX, and then the affect of PMF-1 down regulation on the sensitivity of the tumor cells to DEX was analyzed. MTT method was used to detect cell proliferation, flow cytometry was used to analyze cell cycle,Western blotting method was used to evaluate expression level of glucocorticoids receptor (GR), and HPLC was used to analyze intracellular polyamine content. Results: The transient transfection of Caski cells with siRNA which targets PMF-1 gene can significantly reduce the expression level of PMF-1 protein. Compared with the control cells, treating PMF-1 down-regulated Caski cells with DEX can more effectively inhibit cell proliferation（P<0.01), up regulate GR expression, arrest cell cycle at G2 stage（P<0.01), and also significantly reduce intracellular polyamine level（P<0.01). Conclusion：Inhibiting PMF-1 expression can enhance antitumor pharmacological activity of DEX against human cervical cancer cells, and the underlying mechanism may be related with enhanced cell cycle inhibition and decreased intracellular polyamine level.
Objective: To investigate the influence of inhibiting expression of polyamine-modulated factor (PMF-1) on the antitumor effect of glucocorticoid dexamethasone (DEX) in human cervical cancer Caski cells. Methods: siRNAs which target human PMF-1 gene were designed and synthesized, and their effect on the expression of PMF-1 in Caski cells was evaluated by Western blotting. The PMF-1 down-regulated and control Caski cells were treated with DEX, and then the affect of PMF-1 down regulation on the sensitivity of the tumor cells to DEX was analyzed. MTT method was used to detect cell proliferation, flow cytometry was used to analyze cell cycle,Western blotting method was used to evaluate expression level of glucocorticoids receptor (GR), and HPLC was used to analyze intracellular polyamine content. Results: The transient transfection of Caski cells with siRNA which targets PMF-1 gene can significantly reduce the expression level of PMF-1 protein. Compared with the control cells, treating PMF-1 down-regulated Caski cells with DEX can more effectively inhibit cell proliferation（P<0.01), up regulate GR expression, arrest cell cycle at G2 stage（P<0.01), and also significantly reduce intracellular polyamine level（P<0.01). Conclusion：Inhibiting PMF-1 expression can enhance antitumor pharmacological activity of DEX against human cervical cancer cells, and the underlying mechanism may be related with enhanced cell cycle inhibition and decreased intracellular polyamine level.
2018, 25(7):716-720.
DOI: 10.3872/j.issn.1007-385X.2018.07.010
Abstract:
Objective:To investigate the role of FOXO3a in hypoxia-induced cisplatin (DDP) resistance in osteosarcoma cells. Methods:The FOXO3a expression was detected by RT-PCR and Western blotting in osteosarcoma U-2OS cell line under normoxia and hypoxia conditions. The effects of HIF-1α-siRNA and FOXO3a-siRNA on the expressions of HIF-1αand FOXO3a were detected by Western blotting. CCK-8 and Annexin V/PI assays were used to detect the function of FOXO3a in hypoxia-induced DDP resistance of U-20S cells. Results: Hypoxia could significantly increase the mRNA and protein levels of FOXO3a in U-2OS cells (All P<0.05). The expression of FOXO3a was regulated by HIF-1α; compared with control group and HIF-1α -NC group, the FOX03a protein expression was significantly down-regulated in HIF-1α-siRNA group [(0.38±0.03) vs (0.89±0.08)，(0.91±0.07), all P<0.01]. Under hypoxia condition,FOXO3a-siRNA could decrease the tolerance of U-2OS cells to DDP [(38.50±2.83)% vs (61.75±5.73)%, P<0.01], and increase DDP-induced apoptosis of U-2OS cells [(73.41±6.13)% vs (32.38±2.23)%, (55.89±4.46)%, All P<0.05]. Conclusions: Hypoxia significantly enhanced DDP-resistance of U-2OS cells by increasing FOXO3a expression in a HIF-1-dependent manner.
Objective:To investigate the role of FOXO3a in hypoxia-induced cisplatin (DDP) resistance in osteosarcoma cells. Methods:The FOXO3a expression was detected by RT-PCR and Western blotting in osteosarcoma U-2OS cell line under normoxia and hypoxia conditions. The effects of HIF-1α-siRNA and FOXO3a-siRNA on the expressions of HIF-1αand FOXO3a were detected by Western blotting. CCK-8 and Annexin V/PI assays were used to detect the function of FOXO3a in hypoxia-induced DDP resistance of U-20S cells. Results: Hypoxia could significantly increase the mRNA and protein levels of FOXO3a in U-2OS cells (All P<0.05). The expression of FOXO3a was regulated by HIF-1α; compared with control group and HIF-1α -NC group, the FOX03a protein expression was significantly down-regulated in HIF-1α-siRNA group [(0.38±0.03) vs (0.89±0.08)，(0.91±0.07), all P<0.01]. Under hypoxia condition,FOXO3a-siRNA could decrease the tolerance of U-2OS cells to DDP [(38.50±2.83)% vs (61.75±5.73)%, P<0.01], and increase DDP-induced apoptosis of U-2OS cells [(73.41±6.13)% vs (32.38±2.23)%, (55.89±4.46)%, All P<0.05]. Conclusions: Hypoxia significantly enhanced DDP-resistance of U-2OS cells by increasing FOXO3a expression in a HIF-1-dependent manner.
PENG Xiaobo
,
GUO Chengtao
,
YING Mingzhen
,
LI Jie
,
SONG Lele
,
WU Yanjun
,
ZHAN Lixing
,
ZHAN Xianbao
2018, 25(7):721-725.
DOI: 10.3872/j.issn.1007-385X.2018.07.011
Abstract:
Objective: To construct a hsa-microRNA-224(miR-224) lentiviral expression vector and to establish pancreatic mucinous cystadenocarcinoma MCC1 cell line with stable miR-224 over-expression. Methods: Pri-miR-224 gene fragment was designed and amplified by quantitative real-time polymerase chain reaction (qRT-PCR), and then loaded into GV369 lentiviral vectors (GV369-miR-224) by gene recombination technology. GV369-miR-224 lentivrial expression vectors were then identified by PCR and DNA sequencing.The GV369-miR-224 vector fluid was then used to infect pancreatic mucinous cystadenocarcinoma MCC1 cell line to establish the MCC1 cell line stably over-expressing miR-224. The transfection efficiency of GV369-NC and GV369-miR-224 was observed under fluorescence microscopy; and the expression levels of miR-224 in MCC1, GV369-miR-224-MCC1 and GV369-NC-MCC1 cell lines were detected by RT-PCR. Results: The GV369-miR-224 lentiviral vectors were successfully constructed. GV369-miR-224-MCC1 and GV369-NC-MCC1 cells all emit green fluorescence under the fluorescence microscope. The expression level of miR-224 in GV369-miR-224-MCC1 cell group was significantly higher than that in negative control GV369-miR-224-MCC1 group and blank control MCC1 cell group (23.45±1.94，1.46±0.1 and 2.11±0.38, P<0.01), however, there was no significant difference between the two control groups (P>0.05). Conclusion: A pancreatic mucinous cystadenocarcinoma MCC1 cell line with stable miR-224 over-expression was successfully established, and this will provide a new cell model for exploring the function and pathogenesis of miR-224 in pancreatic mucinous cystadenocarcinoma.
Objective: To construct a hsa-microRNA-224(miR-224) lentiviral expression vector and to establish pancreatic mucinous cystadenocarcinoma MCC1 cell line with stable miR-224 over-expression. Methods: Pri-miR-224 gene fragment was designed and amplified by quantitative real-time polymerase chain reaction (qRT-PCR), and then loaded into GV369 lentiviral vectors (GV369-miR-224) by gene recombination technology. GV369-miR-224 lentivrial expression vectors were then identified by PCR and DNA sequencing.The GV369-miR-224 vector fluid was then used to infect pancreatic mucinous cystadenocarcinoma MCC1 cell line to establish the MCC1 cell line stably over-expressing miR-224. The transfection efficiency of GV369-NC and GV369-miR-224 was observed under fluorescence microscopy; and the expression levels of miR-224 in MCC1, GV369-miR-224-MCC1 and GV369-NC-MCC1 cell lines were detected by RT-PCR. Results: The GV369-miR-224 lentiviral vectors were successfully constructed. GV369-miR-224-MCC1 and GV369-NC-MCC1 cells all emit green fluorescence under the fluorescence microscope. The expression level of miR-224 in GV369-miR-224-MCC1 cell group was significantly higher than that in negative control GV369-miR-224-MCC1 group and blank control MCC1 cell group (23.45±1.94，1.46±0.1 and 2.11±0.38, P<0.01), however, there was no significant difference between the two control groups (P>0.05). Conclusion: A pancreatic mucinous cystadenocarcinoma MCC1 cell line with stable miR-224 over-expression was successfully established, and this will provide a new cell model for exploring the function and pathogenesis of miR-224 in pancreatic mucinous cystadenocarcinoma.
MENG Lingjiaoa
,
DING Pinganb
,
JU Yingchaoc
,
LIU Feia
,
LIU Shinaa
,
LIU Sihuaa
,
CHANG Shenga
,
GU Linaa
,
SANG Meixianga
2018, 25(7):726-732.
DOI: 10.3872/j.issn.1007-385X.2018.07.012
Abstract:
Objective: To investigate the expression of ciRS-7 in esophageal squamous cell carcinoma (ESCC) and its effect on the cellular proliferation, migration and invasion. Methods: The cancer tissues and paired adjacent normal tissues from 60 ESCC patients treated in the Fourth Hospital of Hebei Medical University between May, 2016 and April, 2017 were selected for this study. The expressions of ciRS-7 were detected by qRT-PCR. After over-expressing or silencing of ciRS-7, the proliferation of ESCC cell line TE1 was measured by CCK-8 assay; and the migration and invasion were tested by wound healing assay and Transwell invasion assay，respectively.Finally, the effect was validated via animal experiment. Results: CiRS-7 was highly expressed in ESCC tissues (P<0.05), and its expression level was closely related to pathological grade and lymph node metastasis (P<0.05). Over-expression of ciRS-7 significantly increased the proliferation, migration and invasion (all P<0.05) of TE1 cells; while silencing of ciRS-7 remarkably suppressed the proliferation,migration and invasion (all P<0.05). Conclusion: CiRS-7 was up-regulated in ESCC and could enhance ESCC cell proliferation,migration and invasion, suggesting that ciRS-7 could be used as a potential target for the diagnosis and treatment of ESCC.
Objective: To investigate the expression of ciRS-7 in esophageal squamous cell carcinoma (ESCC) and its effect on the cellular proliferation, migration and invasion. Methods: The cancer tissues and paired adjacent normal tissues from 60 ESCC patients treated in the Fourth Hospital of Hebei Medical University between May, 2016 and April, 2017 were selected for this study. The expressions of ciRS-7 were detected by qRT-PCR. After over-expressing or silencing of ciRS-7, the proliferation of ESCC cell line TE1 was measured by CCK-8 assay; and the migration and invasion were tested by wound healing assay and Transwell invasion assay，respectively.Finally, the effect was validated via animal experiment. Results: CiRS-7 was highly expressed in ESCC tissues (P<0.05), and its expression level was closely related to pathological grade and lymph node metastasis (P<0.05). Over-expression of ciRS-7 significantly increased the proliferation, migration and invasion (all P<0.05) of TE1 cells; while silencing of ciRS-7 remarkably suppressed the proliferation,migration and invasion (all P<0.05). Conclusion: CiRS-7 was up-regulated in ESCC and could enhance ESCC cell proliferation,migration and invasion, suggesting that ciRS-7 could be used as a potential target for the diagnosis and treatment of ESCC.
2018, 25(7):733-736.
DOI: 10.3872/j.issn.1007-385X.2018.07.013
Abstract:
[摘要] 免疫检查点通过双信号机制调控肿瘤微环境中最主要的免疫细胞——T淋巴细胞的免疫应答活性而发挥作用。这些分子主要分为两类，一类是免疫球蛋白（immune globulin, Ig）超家族，另一类是肿瘤坏死因子（tumor necrosis factor，TNF）配体/受体对。随着研究的深入，新的免疫检查点靶点不断涌现，其中，CD40、CD27、4-1BB、OX40 及VISTA等在实体瘤治疗中具有良好前景。负向免疫检查点(negative checkpoint regulators, NCRs)也逐渐受到重视，更多新兴免疫检查点分子正在临床试验阶段，低反应率及耐药性是新靶点研究的瓶颈。本文就免疫检查点靶点的特点、部分研究中的免疫检查点新靶点、新兴免疫检查点靶点研究前景与挑战等热点问题作一综述。
[摘要] 免疫检查点通过双信号机制调控肿瘤微环境中最主要的免疫细胞——T淋巴细胞的免疫应答活性而发挥作用。这些分子主要分为两类，一类是免疫球蛋白（immune globulin, Ig）超家族，另一类是肿瘤坏死因子（tumor necrosis factor，TNF）配体/受体对。随着研究的深入，新的免疫检查点靶点不断涌现，其中，CD40、CD27、4-1BB、OX40 及VISTA等在实体瘤治疗中具有良好前景。负向免疫检查点(negative checkpoint regulators, NCRs)也逐渐受到重视，更多新兴免疫检查点分子正在临床试验阶段，低反应率及耐药性是新靶点研究的瓶颈。本文就免疫检查点靶点的特点、部分研究中的免疫检查点新靶点、新兴免疫检查点靶点研究前景与挑战等热点问题作一综述。
2018, 25(7):737-741.
DOI: 10.3872/j.issn.1007-385X.2018.07.014
Abstract:
[摘要]免疫检查点为T 细胞提供抑制信号，造成肿瘤细胞免疫逃，为肿瘤治疗提供了全新的理念。程序性死亡受体（programmed cell death-1，PD-1）/程序性死亡受体配体-1（programmed death legend 1，PD-L1）成为最具发展前景的靶点,PD-1/PD-L1抗体在治疗黑色素瘤和非小细胞肺癌（NSCLC）中表现出显著的抗瘤效应和良好的安全性。在进展期胃癌患者外周血以及癌组织中PD-L1 均高表达，与多种病理特征存在一定正相关，往往是患者不良预后的预测指标。相关临床试验表明，应用PD-1/PD-L1抗体可使胃癌或胃食管交界癌患者受益，且无不可耐受副反应发生。而多种因素均与PD-1/PD-L1 表达相关，若调节这些因素的药物与PD-1/PD-L1 抑制剂联合应用，将有可能进一步提高胃癌的疗效。
[摘要]免疫检查点为T 细胞提供抑制信号，造成肿瘤细胞免疫逃，为肿瘤治疗提供了全新的理念。程序性死亡受体（programmed cell death-1，PD-1）/程序性死亡受体配体-1（programmed death legend 1，PD-L1）成为最具发展前景的靶点,PD-1/PD-L1抗体在治疗黑色素瘤和非小细胞肺癌（NSCLC）中表现出显著的抗瘤效应和良好的安全性。在进展期胃癌患者外周血以及癌组织中PD-L1 均高表达，与多种病理特征存在一定正相关，往往是患者不良预后的预测指标。相关临床试验表明，应用PD-1/PD-L1抗体可使胃癌或胃食管交界癌患者受益，且无不可耐受副反应发生。而多种因素均与PD-1/PD-L1 表达相关，若调节这些因素的药物与PD-1/PD-L1 抑制剂联合应用，将有可能进一步提高胃癌的疗效。
2018, 25(7):742-746.
DOI: 10.3872/j.issn.1007-385X.2018.07.015
Abstract:
[摘要]在天然免疫应答尤其是抗病毒天然免疫应答中，维甲酸诱导基因-I（retinoic acid inducible gene I,RIG-I）是重要的胞内病毒RNA模式识别受体，其通过结合和识别病毒来源的RNA进而活化下游RIG-I 信号通路，从而激发炎症因子和I 型干扰素的表达，实现抗病毒天然免疫应答的启动。然而，新近研究表明，在肿瘤发生发展的过程中，RIG-I 亦可发挥重要的调控作用。在肿瘤进展的不同病理阶段，RIG-I 可发挥抑制或促进肿瘤进展的功能。本文就RIG-I 在不同肿瘤及其发生发展不同阶段所发挥的抑癌基因或促癌基因样作用的研究进展作一综述。
[摘要]在天然免疫应答尤其是抗病毒天然免疫应答中，维甲酸诱导基因-I（retinoic acid inducible gene I,RIG-I）是重要的胞内病毒RNA模式识别受体，其通过结合和识别病毒来源的RNA进而活化下游RIG-I 信号通路，从而激发炎症因子和I 型干扰素的表达，实现抗病毒天然免疫应答的启动。然而，新近研究表明，在肿瘤发生发展的过程中，RIG-I 亦可发挥重要的调控作用。在肿瘤进展的不同病理阶段，RIG-I 可发挥抑制或促进肿瘤进展的功能。本文就RIG-I 在不同肿瘤及其发生发展不同阶段所发挥的抑癌基因或促癌基因样作用的研究进展作一综述。
2018, 25(7):747-751.
DOI: 10.3872/j.issn.1007-385X.2018.07.016
Abstract:
[摘要] 个体化多肽疫苗（personalized peptide vaccines，PPVs）是指根据肿瘤患者的个体遗传基因结构和功能差异，从一系列候选多肽中选出至多４种与人类白细胞抗原A1 亚型（HLA-A1）匹配的多肽，制作成的肿瘤疫苗。与常规多肽疫苗相比较，PPVs能诱导更强大和更快捷的抗肿瘤免疫力。现有临床研究结果显示，PPVs 在去势抵抗性前列腺癌(castration-resistant prostate cancer，CRPC)免疫治疗中具有良好的应用前景，可明显改善无进展生存期和总体生存期。目前，PPVs仍处于临床研究阶段，与真正的临床应用尚存在一定距离，对于治疗对象的选择、疗效的评估以及联合用药的价值等问题均有待进一步的探索。
[摘要] 个体化多肽疫苗（personalized peptide vaccines，PPVs）是指根据肿瘤患者的个体遗传基因结构和功能差异，从一系列候选多肽中选出至多４种与人类白细胞抗原A1 亚型（HLA-A1）匹配的多肽，制作成的肿瘤疫苗。与常规多肽疫苗相比较，PPVs能诱导更强大和更快捷的抗肿瘤免疫力。现有临床研究结果显示，PPVs 在去势抵抗性前列腺癌(castration-resistant prostate cancer，CRPC)免疫治疗中具有良好的应用前景，可明显改善无进展生存期和总体生存期。目前，PPVs仍处于临床研究阶段，与真正的临床应用尚存在一定距离，对于治疗对象的选择、疗效的评估以及联合用药的价值等问题均有待进一步的探索。
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.