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Volume 28,Issue 3,2021 Table of Contents
2021, 28(3):215-224.
DOI: 10.3872/j.issn.1007-385X.2021.03.001
Abstract:
Autophagy, as an important intracellular metabolic pathway, has been proved to be ubiquitous in many kinds of cells. Its functional impairment can easily cause lots of diseases, such as cancer, leukemia, liver disease, diabetes and heart disease. In particular,autophagy is important for the development, differentiation and regulation of immune function of T lymphocytes. Abnormal autophagy of T lymphocytes can cause immune dysfunction and lead to diseases, such as inflammation, infection and autoimmunity. In view of the important role of autophagy in regulating T lymphocyte function and disease, this article illustrates the research progress on autophagy regulating the homeostasis, survival, proliferation, senescence, metabolism, immune function of T lymphocytes and many diseases,including tumors, in recent years.
Autophagy, as an important intracellular metabolic pathway, has been proved to be ubiquitous in many kinds of cells. Its functional impairment can easily cause lots of diseases, such as cancer, leukemia, liver disease, diabetes and heart disease. In particular,autophagy is important for the development, differentiation and regulation of immune function of T lymphocytes. Abnormal autophagy of T lymphocytes can cause immune dysfunction and lead to diseases, such as inflammation, infection and autoimmunity. In view of the important role of autophagy in regulating T lymphocyte function and disease, this article illustrates the research progress on autophagy regulating the homeostasis, survival, proliferation, senescence, metabolism, immune function of T lymphocytes and many diseases,including tumors, in recent years.
2021, 28(3):225-231.
DOI: 10.3872/j.issn.1007-385X.2021.03.002
Abstract:
Objective: To investigate whether AP1903, a small-molecule chemical inducer, can terminate the cytotoxicity of CD19CAR-T cells over-expressing iCasp9 suicide gene in vivo and in vitro. Methods: CD19CAR-T cells over-expressing iCasp9 (iCasp9-CD19CAR-T) were constructed and co-incubated with AP1903. Then, the cell phenotype and apoptosis were detected by Flow cytometry, and the iCasp9/CID suicide gene system was verified on K562 and T cells, respectively. The cytotoxicity of iCasp9-CD19CAR-T cells was detected in vivo (survival rate of NCG mice bearing Raji cell transplanted xenograft) and in vitro (cell killing function was detected by Flow cytometry) under the administration of AP1903. Results: Compared with CD19CAR-T cells, iCasp9-CD19CAR-T cells showed in significant difference in proliferation, phenotype and cytotoxicity both in vitro and in vivo (all P>0.05). At 2 h after AP1903 administration, the apoptosis rates of K562 and T cells co-expressing iCasp9 and CD19CAR were (33.8±0.9)% and (27.95±0.35)%, respectively; and at 24 h after AP1903 administration, the apoptosis rates reached 100% in both cell lines. The in vitro cytotoxicity of iCasp9-CD19CAR-T cells induced by AP1903 was significantly lower than that without AP1903 treatment (P<0.01); the 60-day survival rate of mice bearing Raji cell transplanted tumor treated with AP1903-induced iCasp9-CD19CAR-T cells was also significantly lower than those treated with iCasp9-CD19CAR-T cells alone (P<0.01). Conclusion: AP1903 can effectively terminate the cytotoxicity of CD19CAR-T cells over-expressing iCasp9 suicide gene in vitro and in vivo.
Objective: To investigate whether AP1903, a small-molecule chemical inducer, can terminate the cytotoxicity of CD19CAR-T cells over-expressing iCasp9 suicide gene in vivo and in vitro. Methods: CD19CAR-T cells over-expressing iCasp9 (iCasp9-CD19CAR-T) were constructed and co-incubated with AP1903. Then, the cell phenotype and apoptosis were detected by Flow cytometry, and the iCasp9/CID suicide gene system was verified on K562 and T cells, respectively. The cytotoxicity of iCasp9-CD19CAR-T cells was detected in vivo (survival rate of NCG mice bearing Raji cell transplanted xenograft) and in vitro (cell killing function was detected by Flow cytometry) under the administration of AP1903. Results: Compared with CD19CAR-T cells, iCasp9-CD19CAR-T cells showed in significant difference in proliferation, phenotype and cytotoxicity both in vitro and in vivo (all P>0.05). At 2 h after AP1903 administration, the apoptosis rates of K562 and T cells co-expressing iCasp9 and CD19CAR were (33.8±0.9)% and (27.95±0.35)%, respectively; and at 24 h after AP1903 administration, the apoptosis rates reached 100% in both cell lines. The in vitro cytotoxicity of iCasp9-CD19CAR-T cells induced by AP1903 was significantly lower than that without AP1903 treatment (P<0.01); the 60-day survival rate of mice bearing Raji cell transplanted tumor treated with AP1903-induced iCasp9-CD19CAR-T cells was also significantly lower than those treated with iCasp9-CD19CAR-T cells alone (P<0.01). Conclusion: AP1903 can effectively terminate the cytotoxicity of CD19CAR-T cells over-expressing iCasp9 suicide gene in vitro and in vivo.
2021, 28(3):232-238.
DOI: 10.3872/j.issn.1007-385X.2021.03.003
Abstract:
Objective: To explore the anti-tumor activity of MUC16-targeted chimeric antigen receptor modified NK-92 (CARNK-92) cells against ovarian cancer. Methods: The expression of MUC16 in surgically resected tumor tissues of 15 patients with ovarian cancer treated in the Department of Obstetrics and Gynecology of Qingyang Hospital of Traditional Chinese Medicine and 4 ovarian tumor cell lines was detected by Immunohistochemistry and Flow cytometry. MUC CAR sequence was synthesized by gene synthesis, and its lentivirus expression vector were constructed. CARNK-92 cells targeting MUC16 (MUC-BBz) were obtained by lentivirus infection. The expression of CD107a in MUC-BBz was detected by Flow cytometry. The activation of MUC-BBz cells and its cytotoxicity against SKOV3 target cells were characterized by the release of LDH assay. The xenograft nude mouse model of SKOV3 cells was established to verify the in vivo anti-tumor activity of MUC-BBz cells. Results: MUC16 was highly expressed in ovarian cancer tissues and human ovarian cancer cells. MUC-BBz was successfully constructed by infecting NK-92 cells with lentivirus, with a positive rate of (42.79±2.58)%. MUC-BBz could be specifically activated by MUC16 over-expressing tumor cells. After co-incubation of effector cells and target cells, the expression of CD107a on MUC-BBz was upregulated significantly (P<0.01), and the ability of MUC-BBz secreting cytokines IFN-γ and perforin also increased (all P<0.01). The LDH test indicated that with the increase of effector-target ratio, the cytotoxicity of MUC-BBz against 4 ovarian cancer cells (hey,COC1, SKOV3 andA2780) also significantly enhanced. The results of transplanted tumor model showed that transfusion of MUC-BBz could significantly inhibit the growth of SKOV3 xenograft in mice (P<0.01). Conclusion: The CARNK-92 cells can significantly inhibit the growth of ovarian cancer cells in vitro and in vivo, which provides an important basis for further evaluation of its clinical application.
Objective: To explore the anti-tumor activity of MUC16-targeted chimeric antigen receptor modified NK-92 (CARNK-92) cells against ovarian cancer. Methods: The expression of MUC16 in surgically resected tumor tissues of 15 patients with ovarian cancer treated in the Department of Obstetrics and Gynecology of Qingyang Hospital of Traditional Chinese Medicine and 4 ovarian tumor cell lines was detected by Immunohistochemistry and Flow cytometry. MUC CAR sequence was synthesized by gene synthesis, and its lentivirus expression vector were constructed. CARNK-92 cells targeting MUC16 (MUC-BBz) were obtained by lentivirus infection. The expression of CD107a in MUC-BBz was detected by Flow cytometry. The activation of MUC-BBz cells and its cytotoxicity against SKOV3 target cells were characterized by the release of LDH assay. The xenograft nude mouse model of SKOV3 cells was established to verify the in vivo anti-tumor activity of MUC-BBz cells. Results: MUC16 was highly expressed in ovarian cancer tissues and human ovarian cancer cells. MUC-BBz was successfully constructed by infecting NK-92 cells with lentivirus, with a positive rate of (42.79±2.58)%. MUC-BBz could be specifically activated by MUC16 over-expressing tumor cells. After co-incubation of effector cells and target cells, the expression of CD107a on MUC-BBz was upregulated significantly (P<0.01), and the ability of MUC-BBz secreting cytokines IFN-γ and perforin also increased (all P<0.01). The LDH test indicated that with the increase of effector-target ratio, the cytotoxicity of MUC-BBz against 4 ovarian cancer cells (hey,COC1, SKOV3 andA2780) also significantly enhanced. The results of transplanted tumor model showed that transfusion of MUC-BBz could significantly inhibit the growth of SKOV3 xenograft in mice (P<0.01). Conclusion: The CARNK-92 cells can significantly inhibit the growth of ovarian cancer cells in vitro and in vivo, which provides an important basis for further evaluation of its clinical application.
2021, 28(3):239-246.
DOI: 10.3872/j.issn.1007-385X.2021.03.004
Abstract:
Objective: To explore the effect of anti-ENO1 (enolase 1) antibody and metformin (MET) treatment on the proliferation,migration, invasion and stemness of cetuximab (CTX) -resistant non-small cell lung cancer (NSCLC) cells through targeting cancer stem cells and the possible mechanism. Methods: 10 mmol/L MET combined with 40 μg/ml anti-ENO1 antibody was used to treat CTX (35 μg/ml)-resistant NSCLC A549 cells for 4 d, and the effects of combined treatment on A549 cells were detected with proliferation experiment, colony formation assay, migration and invasion experiments and methylcellulose ball formation experiment. In the meanwhile, FCM was used to detect the effects of CTX, MET and anti-ENO1 antibody single-drug treatment as well as the three-drug combination treatment on ALDH+ and CD44+ lung cancer stem cell subsets. Results: CTX combined with MET and anti-ENO1 antibody treatment significantly inhibited the proliferation, migration, invasion and self-renewal capacity of A549 cells. FCM analysis found that MET could significantly inhibit ALDH+ stem cell subpopulations, while anti-ENO1 antibody could significantly inhibit CD44+ stem cell subpopulations, and the three-drug combination treatment could simultaneously suppress ALDH+ and CD44+ stem cell subpopulations. Conclusion: MET and anti-ENO1 antibody respectively target ALDH+ and CD44+ cancer stem cell subsets, and the combined treatment of MET and anti-ENO1 antibody can effectively reverse the resistance of A549 cells to CTX, and thereby more effectively inhibiting stemness, proliferation, metastasis of A549 cells and tumor recurrence.
Objective: To explore the effect of anti-ENO1 (enolase 1) antibody and metformin (MET) treatment on the proliferation,migration, invasion and stemness of cetuximab (CTX) -resistant non-small cell lung cancer (NSCLC) cells through targeting cancer stem cells and the possible mechanism. Methods: 10 mmol/L MET combined with 40 μg/ml anti-ENO1 antibody was used to treat CTX (35 μg/ml)-resistant NSCLC A549 cells for 4 d, and the effects of combined treatment on A549 cells were detected with proliferation experiment, colony formation assay, migration and invasion experiments and methylcellulose ball formation experiment. In the meanwhile, FCM was used to detect the effects of CTX, MET and anti-ENO1 antibody single-drug treatment as well as the three-drug combination treatment on ALDH+ and CD44+ lung cancer stem cell subsets. Results: CTX combined with MET and anti-ENO1 antibody treatment significantly inhibited the proliferation, migration, invasion and self-renewal capacity of A549 cells. FCM analysis found that MET could significantly inhibit ALDH+ stem cell subpopulations, while anti-ENO1 antibody could significantly inhibit CD44+ stem cell subpopulations, and the three-drug combination treatment could simultaneously suppress ALDH+ and CD44+ stem cell subpopulations. Conclusion: MET and anti-ENO1 antibody respectively target ALDH+ and CD44+ cancer stem cell subsets, and the combined treatment of MET and anti-ENO1 antibody can effectively reverse the resistance of A549 cells to CTX, and thereby more effectively inhibiting stemness, proliferation, metastasis of A549 cells and tumor recurrence.
2021, 28(3):247-253.
DOI: 10.3872/j.issn.1007-385X.2021.03.005
Abstract:
Objective: To explore the effect and mechanism of splicing factor 3b subunit 6 (SF3b6) on the proliferation, apoptosis,invasion and migration of gastric cancer cells. Methods: Tissue microarrays were used to detect the expression of SF3b6 in gastric cancer tissues and adjacent tissues. WB and qPCR were used to detect the expression of SF3b6 in normal immortalized gastric epithelial cells (GES-1) and gastric cancer cell lines (HGC27, AGS, BGC823, MGC803, SGC7901, MKN45). AGS and MGC803 cells were transfected with SF3b6 siRNA, and BGC823 and SGC7901 cells were transfected with SF3b6 over-expression plasmid for functional experiments. CCK-8 assay was used to detect the regulation of SF3b6 on the proliferation of gastric cancer cells; Transwell migration and invasion experiments were used to detect the effect of SF3b6 on the migration and invasion of gastric cancer cells; Flow cytometry was used to detect cell apoptosis; and WB was adopted to detect expressions of apoptosis and migration-related molecules and MAPK signaling pathway associated proteins. Results: The expression level of SF3b6 in gastric cancer MGC803 and AGS cells was significantly higher while in BGC823 and SGC7901 cells was significantly lower than that in normal gastric epithelial GES-1 cells (P<0.05 or P<0.01). SF3b6 knockdown inhibited the proliferation, migration and invasion, but promoted cell apoptosis of gastric cancer cell lines AGS and MGC803 (P<0.05 or P<0.01); However, over-expression of SF3b6 promoted the proliferation, migration and invasion of gastric cancer cell lines BGC823 and SGC7901 (P<0.05 or P<0.01). Mechanism study showed that SF3b6 knockdown promoted the activation of JNK and p38 and expression of apoptosis-related protein cleaved caspase-9, cleaved PARP and Bax (P<0.05 or P<0.01), and meanwhile inhibited the process of epithelial to mesenchymal transition (EMT) in gastric cancer cells. Conclusion:The splicing factor SF3b6 enhances cell proliferation and migration via MAPK signaling pathway, thereby promoting tumor progression.
Objective: To explore the effect and mechanism of splicing factor 3b subunit 6 (SF3b6) on the proliferation, apoptosis,invasion and migration of gastric cancer cells. Methods: Tissue microarrays were used to detect the expression of SF3b6 in gastric cancer tissues and adjacent tissues. WB and qPCR were used to detect the expression of SF3b6 in normal immortalized gastric epithelial cells (GES-1) and gastric cancer cell lines (HGC27, AGS, BGC823, MGC803, SGC7901, MKN45). AGS and MGC803 cells were transfected with SF3b6 siRNA, and BGC823 and SGC7901 cells were transfected with SF3b6 over-expression plasmid for functional experiments. CCK-8 assay was used to detect the regulation of SF3b6 on the proliferation of gastric cancer cells; Transwell migration and invasion experiments were used to detect the effect of SF3b6 on the migration and invasion of gastric cancer cells; Flow cytometry was used to detect cell apoptosis; and WB was adopted to detect expressions of apoptosis and migration-related molecules and MAPK signaling pathway associated proteins. Results: The expression level of SF3b6 in gastric cancer MGC803 and AGS cells was significantly higher while in BGC823 and SGC7901 cells was significantly lower than that in normal gastric epithelial GES-1 cells (P<0.05 or P<0.01). SF3b6 knockdown inhibited the proliferation, migration and invasion, but promoted cell apoptosis of gastric cancer cell lines AGS and MGC803 (P<0.05 or P<0.01); However, over-expression of SF3b6 promoted the proliferation, migration and invasion of gastric cancer cell lines BGC823 and SGC7901 (P<0.05 or P<0.01). Mechanism study showed that SF3b6 knockdown promoted the activation of JNK and p38 and expression of apoptosis-related protein cleaved caspase-9, cleaved PARP and Bax (P<0.05 or P<0.01), and meanwhile inhibited the process of epithelial to mesenchymal transition (EMT) in gastric cancer cells. Conclusion:The splicing factor SF3b6 enhances cell proliferation and migration via MAPK signaling pathway, thereby promoting tumor progression.
WANG Yitong
,
LU Hongjian
,
KONG Yixuan
,
SU Jinghui
,
LIU Yutan
,
ZHANG Ronghua
,
HOU Xiaoli
,
ZHANG Guangling
2021, 28(3):254-260.
DOI: 10.3872/j.issn.1007-385X.2021.03.006
Abstract:
Objective: To explore the effect of CAAP1 on apoptosis, proliferation, migration and invasion of hepatocellular carcinoma (HCC) HepG2 cells and its mechanism. Methods:The pcDNA3/CAAP1 (CAAP1 over-expression) and pSilencer 2.1-U6 neo/shR-CAAP1 (CAAP1 knockdown) plasmids were constructed and transfected into HepG2 cells. The mRNA and protein levels of CAAP1 were detected by qPCR and WB, respectively. The cells were divided into four groups, namely overexpression control group (pcDNA3),CAAP1 over-expression group (pcDNA3/CAAP1), silence control group (pSilencer 2.1-U6 neo, pSilencer) and CAAP1 silence group (pSilencer 2.1-U6 neo/shR-CAAP1, shR-CAAP1). Flow cytometry was used to analyze the apoptosis, and WB was used to detect the protein expression of cleaved caspase 3 in each group. CCK-8 assay was used to detect the proliferation of HepG2 cells, Colony formation assay was used to detect the clonogenesis, and Transwell assay and wound healing assay were used to detect the invasion and migration abilities of HepG2 cells in each group. The effect of CAAP1 on overall survival (OS) of HCC patients was analyzed after searching TCGA database. Results: PcDNA3/CAAP1 with CAAP1 over-expression and shR-CAAP1 with CAAP1 knockdown were successfully constructed. It was confirmed that pcDNA3/CAAP1 could increase the mRNA and protein expressions of CAAP1，while shR-CAAP1 could decrease the mRNA and protein expressions of CAAP1 (all P<0.05). The cell apoptotic rate in pcDNA3/CAAP1 group decreased by 32% as compared to pcDNA3 group, and the cleaved caspase 3 protein expression was significantly decreased (all P<0.05); while the cell apoptotic rate in shR-CAAP1 group increased by 73% as compared to pSilencer group, and the cleaved caspase 3 protein expression was significantly increased (all P<0.05). The cell proliferation in pcDNA3/CAAP1 group significantly increased (P<0.05), while the cell proliferation in shR-CAAP1 group significantly decreased (P<0.05). The cell migration number increased by 48%, the cell migration distance increased by 59% (P<0.05) and the cell invasion number increased by 52% in pcDNA3/CAAP1 group (all P<0.05). The cell migration number decreased by 53%, cell migration distance decreased by 29% and cell invasion number decreased by 45% in shR-CAAP1 group (all P<0.05). TCGA database analysis showed that the high expression of CAAP1 was negatively correlated with the OS of HCC patients (P<0.05). Conclusion: CAAP1 can promote the proliferation, migration and invasion of HepG2 cells by inhibiting its apoptosis, and it may be closely related to the occurrence and development of HCC.
Objective: To explore the effect of CAAP1 on apoptosis, proliferation, migration and invasion of hepatocellular carcinoma (HCC) HepG2 cells and its mechanism. Methods:The pcDNA3/CAAP1 (CAAP1 over-expression) and pSilencer 2.1-U6 neo/shR-CAAP1 (CAAP1 knockdown) plasmids were constructed and transfected into HepG2 cells. The mRNA and protein levels of CAAP1 were detected by qPCR and WB, respectively. The cells were divided into four groups, namely overexpression control group (pcDNA3),CAAP1 over-expression group (pcDNA3/CAAP1), silence control group (pSilencer 2.1-U6 neo, pSilencer) and CAAP1 silence group (pSilencer 2.1-U6 neo/shR-CAAP1, shR-CAAP1). Flow cytometry was used to analyze the apoptosis, and WB was used to detect the protein expression of cleaved caspase 3 in each group. CCK-8 assay was used to detect the proliferation of HepG2 cells, Colony formation assay was used to detect the clonogenesis, and Transwell assay and wound healing assay were used to detect the invasion and migration abilities of HepG2 cells in each group. The effect of CAAP1 on overall survival (OS) of HCC patients was analyzed after searching TCGA database. Results: PcDNA3/CAAP1 with CAAP1 over-expression and shR-CAAP1 with CAAP1 knockdown were successfully constructed. It was confirmed that pcDNA3/CAAP1 could increase the mRNA and protein expressions of CAAP1，while shR-CAAP1 could decrease the mRNA and protein expressions of CAAP1 (all P<0.05). The cell apoptotic rate in pcDNA3/CAAP1 group decreased by 32% as compared to pcDNA3 group, and the cleaved caspase 3 protein expression was significantly decreased (all P<0.05); while the cell apoptotic rate in shR-CAAP1 group increased by 73% as compared to pSilencer group, and the cleaved caspase 3 protein expression was significantly increased (all P<0.05). The cell proliferation in pcDNA3/CAAP1 group significantly increased (P<0.05), while the cell proliferation in shR-CAAP1 group significantly decreased (P<0.05). The cell migration number increased by 48%, the cell migration distance increased by 59% (P<0.05) and the cell invasion number increased by 52% in pcDNA3/CAAP1 group (all P<0.05). The cell migration number decreased by 53%, cell migration distance decreased by 29% and cell invasion number decreased by 45% in shR-CAAP1 group (all P<0.05). TCGA database analysis showed that the high expression of CAAP1 was negatively correlated with the OS of HCC patients (P<0.05). Conclusion: CAAP1 can promote the proliferation, migration and invasion of HepG2 cells by inhibiting its apoptosis, and it may be closely related to the occurrence and development of HCC.
2021, 28(3):261-268.
DOI: 10.3872/j.issn.1007-385X.2021.03.007
Abstract:
Objective: To investigate the effect of IL-27 in combination with IL-15 on the anti-tumor effects of NK92 cells and the possible molecular and signaling mechanisms. Methods: NK92 cells with high IL-15 expression (IL-15-NK92 cells) were cultured in different mass concentrations of IL-27 (0, 10, 20, 30 and 60 ng/ml)for 24 h. The effects of IL-27 on IL-15 secretion, migration and proliferation of IL-15-NK92 cells were detected by ELISA, Transwell and CCK-8 assay, respectively. Flow cytometry was used to detect the expression levels of IL-15-NK92 cell surface receptors NKG2D, NKp30 and NKp46, as well as the secretion levels of perforin and granzyme B. LDH method was used to detect the cytotoxic effect of IL-15-NK92 cells on hematologic tumor cells and solid tumor cells, and WB was used to detect the expressions and phosphorylation level of STATs pathway-related proteins. Results: IL-27 at the concentration of 30 ng/ml promoted IL-15-NK92 cells secreting IL-15 (P<0.01), significantly enhanced the cell migration (P<0.05) but inhibited the proliferation of IL-15-NK92 cells (P<0.05). 30 ng/ml IL-27 could significantly promote the expressions of NKG2D, NKp30 and NKp46 on surface of IL-15-NK 92 cells,as well as elevate the secretion of perforin (all P<0.05), but didn’t affect the secretion of granzyme B (P>0.05); moreover, it also significantly enhanced the cytotoxicity of IL-15-NK92 cells against hematologic malignancies and solid tumor cells (P<0.05 or P<0.01), and up-regulated the phosphorylation levels of STAT1, STAT3 and STAT5 (all P<0.01). Conclusion: IL-27 can enhance the cytotoxicity of IL-15-NK92 cells against hematologic tumor cells and solid tumor cells, which might be related with its upregulation of phosphorylation level of STAT1, STAT3 and STAT5 in JAK-STAT pathway and multiple activating receptors in IL-15-NK92 cells.
Objective: To investigate the effect of IL-27 in combination with IL-15 on the anti-tumor effects of NK92 cells and the possible molecular and signaling mechanisms. Methods: NK92 cells with high IL-15 expression (IL-15-NK92 cells) were cultured in different mass concentrations of IL-27 (0, 10, 20, 30 and 60 ng/ml)for 24 h. The effects of IL-27 on IL-15 secretion, migration and proliferation of IL-15-NK92 cells were detected by ELISA, Transwell and CCK-8 assay, respectively. Flow cytometry was used to detect the expression levels of IL-15-NK92 cell surface receptors NKG2D, NKp30 and NKp46, as well as the secretion levels of perforin and granzyme B. LDH method was used to detect the cytotoxic effect of IL-15-NK92 cells on hematologic tumor cells and solid tumor cells, and WB was used to detect the expressions and phosphorylation level of STATs pathway-related proteins. Results: IL-27 at the concentration of 30 ng/ml promoted IL-15-NK92 cells secreting IL-15 (P<0.01), significantly enhanced the cell migration (P<0.05) but inhibited the proliferation of IL-15-NK92 cells (P<0.05). 30 ng/ml IL-27 could significantly promote the expressions of NKG2D, NKp30 and NKp46 on surface of IL-15-NK 92 cells,as well as elevate the secretion of perforin (all P<0.05), but didn’t affect the secretion of granzyme B (P>0.05); moreover, it also significantly enhanced the cytotoxicity of IL-15-NK92 cells against hematologic malignancies and solid tumor cells (P<0.05 or P<0.01), and up-regulated the phosphorylation levels of STAT1, STAT3 and STAT5 (all P<0.01). Conclusion: IL-27 can enhance the cytotoxicity of IL-15-NK92 cells against hematologic tumor cells and solid tumor cells, which might be related with its upregulation of phosphorylation level of STAT1, STAT3 and STAT5 in JAK-STAT pathway and multiple activating receptors in IL-15-NK92 cells.
2021, 28(3):269-274.
DOI: 10.3872/j.issn.1007-385X.2021.03.008
Abstract:
Objective: To investigate the correlation between PD-L1 expression and dMMR related proteins in follicular thyroid carcinoma tissues and its clinical significance. Methods: The postoperative paraffin-embedded tissue samples from 60 patients with thyroid follicular carcinoma were collected from the Second Affiliated Hospital of Fujian Medical University during January 2015 and June 2020. The collected samples were re-confirmed as thyroid follicular carcinoma tissues by Hematoxylin-eosin staining. The expression of PD-L1 and four homologous proteins encoded by four genes (MLH1, MSH2, MSH6, PMS2) in MMR system were detected by immunohistochemistry in the cancer and paracancerous tissues. The relationship between the expression of PD-L1 and depletion of MMR related proteins in thyroid follicular carcinoma tissues and its clinical significance were analyzed. Results: The positive expression rate of PD-L1 was significantly higher in the follicular thyroid carcinoma tissues than that in paracancerous tissues [63.3%(38/60) vs 11.7%(7/60), P<0.05]. The expression of PD-L1 was significantly correlated with tumor diameter, extrathyroidal infiltration, vascular invasion and recurrence (all P<0.05). In the cancer tissue specimens from 60 patients, 24 (40.0%) had expression of four MMR related proteins, which were pMMR tumors, and 36 (60.0%) had depletion of one or more MMR related proteins, which were dMMR tumors. The dMMR-type thyroid follicular carcinoma was significantly correlated with the status of lymph node metastasis and tumor staging (all P<0.05). PD-L1 was positively correlated with the incidence of dMMR, and PD-L1 was an independent risk factor for disease recurrence, while dMMR was associated with a better prognosis. Patients with PD-L1+/pMMR type were associated with higher tumor malignancy, while patients with PD-L1+/dMMR type were not associated with tumor pathological features but may easily benefit from immunotherapy. Conclusion: Positive PD-L1 expression and dMMR highly occur in follicular thyroid carcinoma. PD-L1 is associated with the increased tumor invasion and is an independent risk factor for disease recurrence,while dMMR is an early molecular event in the development of thyroid follicular carcinoma and is associated with better prognosis of patients.
Objective: To investigate the correlation between PD-L1 expression and dMMR related proteins in follicular thyroid carcinoma tissues and its clinical significance. Methods: The postoperative paraffin-embedded tissue samples from 60 patients with thyroid follicular carcinoma were collected from the Second Affiliated Hospital of Fujian Medical University during January 2015 and June 2020. The collected samples were re-confirmed as thyroid follicular carcinoma tissues by Hematoxylin-eosin staining. The expression of PD-L1 and four homologous proteins encoded by four genes (MLH1, MSH2, MSH6, PMS2) in MMR system were detected by immunohistochemistry in the cancer and paracancerous tissues. The relationship between the expression of PD-L1 and depletion of MMR related proteins in thyroid follicular carcinoma tissues and its clinical significance were analyzed. Results: The positive expression rate of PD-L1 was significantly higher in the follicular thyroid carcinoma tissues than that in paracancerous tissues [63.3%(38/60) vs 11.7%(7/60), P<0.05]. The expression of PD-L1 was significantly correlated with tumor diameter, extrathyroidal infiltration, vascular invasion and recurrence (all P<0.05). In the cancer tissue specimens from 60 patients, 24 (40.0%) had expression of four MMR related proteins, which were pMMR tumors, and 36 (60.0%) had depletion of one or more MMR related proteins, which were dMMR tumors. The dMMR-type thyroid follicular carcinoma was significantly correlated with the status of lymph node metastasis and tumor staging (all P<0.05). PD-L1 was positively correlated with the incidence of dMMR, and PD-L1 was an independent risk factor for disease recurrence, while dMMR was associated with a better prognosis. Patients with PD-L1+/pMMR type were associated with higher tumor malignancy, while patients with PD-L1+/dMMR type were not associated with tumor pathological features but may easily benefit from immunotherapy. Conclusion: Positive PD-L1 expression and dMMR highly occur in follicular thyroid carcinoma. PD-L1 is associated with the increased tumor invasion and is an independent risk factor for disease recurrence,while dMMR is an early molecular event in the development of thyroid follicular carcinoma and is associated with better prognosis of patients.
2021, 28(3):275-282.
DOI: 10.3872/j.issn.1007-385X.2021.03.009
Abstract:
Objective: To investigate the expression changes of miR-96 in endometrial cancer tissues and cells, and to explore its effect on tumor malignant phenotypes as well as the possible mechanisms. Methods: From April 2016 to December 2018, 76 cases of endometrial cancer tissues from 76 patients who were surgically treated in the Department of Obstetrics and Gynecology of our hospital were selected for this study. qPCR was used to detect the expression of miR-96 in human endometrial cancer tissues and cells, and thecorrelation between the miR-96 expression and the clinicopathological characteristics of patients was analyzed. miR-96 inhibitor was transfected into human endometrial cancer Ishikawa cells in vitro. After transfection, the expression of miR-96 in Ishikawa cells was detected by qPCR; the tumor biological behaviors of Ishikawa cells were detected by CCK-8 test, Clone formation test, Flow cytometry,Scratch test and Transwell test; and the FOXO1 protein expression in Ishikawa cells was detected by WB. At the same time, Dual luciferase reporter gene assay was used to observe the targeting relationship between miR-96 and FOXO1. Results: The results of qPCR showed that the expression of miR-96 was abnormally high in human endometrial cancer cells (JEC, Ishikawa, HEC-1B) and endometrial cancer tissues (all P<0.01), and the expression of miR-96 was closely related to FIGO stage and lymph node metastasis (all P<0.05). After transfection with miR-96 inhibitor, the expression level of miR-96 in Ishikawa cells decreased significantly (P<0.01),the proliferation activity and clone formation ability decreased significantly (all P<0.01), the apoptotic rate increased significantly (P<0.01), and the scratch healing rate and the number of invasive transmembrane cells decreased significantly (P<0.01). Dual luciferase reporter gene assay showed that miR-96 could directly target FOXO1, and WB showed that miR-96 could negatively regulate FOXO1 protein expression in Ishikawa cells (P<0.01). Conclusion: The expression of miR-96 is abnormally high in endometrial cancer tissues and cells. Inhibiting the expression of miR-96 can inhibit the proliferation, invasion and migration of endometrial cancer cells and promote their apoptosis. The mechanism may be related to the targeted regulation of FOXO1.
Objective: To investigate the expression changes of miR-96 in endometrial cancer tissues and cells, and to explore its effect on tumor malignant phenotypes as well as the possible mechanisms. Methods: From April 2016 to December 2018, 76 cases of endometrial cancer tissues from 76 patients who were surgically treated in the Department of Obstetrics and Gynecology of our hospital were selected for this study. qPCR was used to detect the expression of miR-96 in human endometrial cancer tissues and cells, and thecorrelation between the miR-96 expression and the clinicopathological characteristics of patients was analyzed. miR-96 inhibitor was transfected into human endometrial cancer Ishikawa cells in vitro. After transfection, the expression of miR-96 in Ishikawa cells was detected by qPCR; the tumor biological behaviors of Ishikawa cells were detected by CCK-8 test, Clone formation test, Flow cytometry,Scratch test and Transwell test; and the FOXO1 protein expression in Ishikawa cells was detected by WB. At the same time, Dual luciferase reporter gene assay was used to observe the targeting relationship between miR-96 and FOXO1. Results: The results of qPCR showed that the expression of miR-96 was abnormally high in human endometrial cancer cells (JEC, Ishikawa, HEC-1B) and endometrial cancer tissues (all P<0.01), and the expression of miR-96 was closely related to FIGO stage and lymph node metastasis (all P<0.05). After transfection with miR-96 inhibitor, the expression level of miR-96 in Ishikawa cells decreased significantly (P<0.01),the proliferation activity and clone formation ability decreased significantly (all P<0.01), the apoptotic rate increased significantly (P<0.01), and the scratch healing rate and the number of invasive transmembrane cells decreased significantly (P<0.01). Dual luciferase reporter gene assay showed that miR-96 could directly target FOXO1, and WB showed that miR-96 could negatively regulate FOXO1 protein expression in Ishikawa cells (P<0.01). Conclusion: The expression of miR-96 is abnormally high in endometrial cancer tissues and cells. Inhibiting the expression of miR-96 can inhibit the proliferation, invasion and migration of endometrial cancer cells and promote their apoptosis. The mechanism may be related to the targeted regulation of FOXO1.
2021, 28(3):283-287.
DOI: 10.3872/j.issn.1007-385X.2021.03.010
Abstract:
Objective: To observe the expression of long-chain non-coding RNA (lncRNA) TPTEP1 in bladder cancer tissues and cells, and to observe its effect on the proliferation and invasion of bladder cancer cells and its molecular mechanism. Methods: From August 2017 to October 2019, 43 cases of bladder cancer tissues and paracancer tissues from the patients treated by surgery in the Department Urology, People's Hospital of Dongxihu Distric of Wuhan City. Real-time fluorescence quantitative polymerase chain reaction (qPCR) was used to detect the expression of lncRNA TPTEP1 in bladder cancer tissues and bladder cancer cell lines (T24, BIU87, 5637, J82, UM-UC-3). The bladder cancer cells with the lowest lncRNA TPTEP1 expression were selected as the experimental object, and transfected with the negative control plasmid (the control group) and lncRNA TPTEP1 over-expression plasmid (the experimental group), respectively. The effect of lncRNA TPTEP1 upregulation on cell proliferation and invasion was detected by MTT method and Transwell experiment. Bioinformatics techniques were used to predict the possible target molecules of lncRNA TPTEP1.qPCR and WB were used to detect the expression levels of lncRNA TPTEP1 downstream molecules. Results: Compared with adjacent tissues, the expression of lncRNA TPTEP1 in bladder cancer tissues was down-regulated (P<0.01). Compared with normal bladder epithelial cells, the expression of lncRNA TPTEP1 in bladder cancer cell lines was down-regulated (P<0.05), and its expression in T24 cells was the lowest (P<0.01). Up-regulation of lncRNA TPTEP1 could inhibit the proliferation (P<0.05) and invasion (P<0.01) of T24 cells. Bioinformatics technology showed that lncRNA TPTEP1 could bind with miR-129-5p, and miR-129-5p could bind with EMP3; up-regulating lncRNA TPTEP1 could inhibit the expression of miR-129-5p in T24 cells (P<0.01), and indirectly promote the mRNA and protein expressions of EMP3 (P<0.01) in T24 cells. The expression of MAPK/ERK signaling pathway related proteins such as p-MEK, p-ERK1/2, p-AKT and p-PI3K decreased (P<0.01). Conclusion: Up-regulating the low-expressed lncRNA TPTEP1 in bladder cancer cell lines can inhibit the proliferation and invasion of bladder cancer T24 cells, and its mechanism is related to indirect promotion of EMP3 gene expression by down-regulating the expression of miR-129-5p.
Objective: To observe the expression of long-chain non-coding RNA (lncRNA) TPTEP1 in bladder cancer tissues and cells, and to observe its effect on the proliferation and invasion of bladder cancer cells and its molecular mechanism. Methods: From August 2017 to October 2019, 43 cases of bladder cancer tissues and paracancer tissues from the patients treated by surgery in the Department Urology, People's Hospital of Dongxihu Distric of Wuhan City. Real-time fluorescence quantitative polymerase chain reaction (qPCR) was used to detect the expression of lncRNA TPTEP1 in bladder cancer tissues and bladder cancer cell lines (T24, BIU87, 5637, J82, UM-UC-3). The bladder cancer cells with the lowest lncRNA TPTEP1 expression were selected as the experimental object, and transfected with the negative control plasmid (the control group) and lncRNA TPTEP1 over-expression plasmid (the experimental group), respectively. The effect of lncRNA TPTEP1 upregulation on cell proliferation and invasion was detected by MTT method and Transwell experiment. Bioinformatics techniques were used to predict the possible target molecules of lncRNA TPTEP1.qPCR and WB were used to detect the expression levels of lncRNA TPTEP1 downstream molecules. Results: Compared with adjacent tissues, the expression of lncRNA TPTEP1 in bladder cancer tissues was down-regulated (P<0.01). Compared with normal bladder epithelial cells, the expression of lncRNA TPTEP1 in bladder cancer cell lines was down-regulated (P<0.05), and its expression in T24 cells was the lowest (P<0.01). Up-regulation of lncRNA TPTEP1 could inhibit the proliferation (P<0.05) and invasion (P<0.01) of T24 cells. Bioinformatics technology showed that lncRNA TPTEP1 could bind with miR-129-5p, and miR-129-5p could bind with EMP3; up-regulating lncRNA TPTEP1 could inhibit the expression of miR-129-5p in T24 cells (P<0.01), and indirectly promote the mRNA and protein expressions of EMP3 (P<0.01) in T24 cells. The expression of MAPK/ERK signaling pathway related proteins such as p-MEK, p-ERK1/2, p-AKT and p-PI3K decreased (P<0.01). Conclusion: Up-regulating the low-expressed lncRNA TPTEP1 in bladder cancer cell lines can inhibit the proliferation and invasion of bladder cancer T24 cells, and its mechanism is related to indirect promotion of EMP3 gene expression by down-regulating the expression of miR-129-5p.
2021, 28(3):288-293.
DOI: 10.3872/j.issn.1007-385X.2021.03.011
Abstract:
细胞焦亡（pyroptosis）是新近发现的一种依赖炎性半胱天冬酶（caspase）的促炎程序性细胞死亡方式（regulated cell death，RCD），主要通过gasdermin家族成员发生剪切活化，引起细胞膜穿孔和细胞内容物释放的过程。Gasdermin E(GSDME)是gasdermin家族的主要成员之一，近来研究发现在几种常见的肿瘤中常因其启动子甲基化而低表达，进而增强了肿瘤的增殖和转移能力；分析其结构和功能显示，GSDME可被激活态的caspase-3切割并形成具有造孔活性的GSDME-N末端结构域，从而诱导肿瘤细胞发生焦亡，介导肿瘤细胞死亡。本文就GSDME介导焦亡的机制及其与肿瘤发生发展的关系作一综述，以期提出新的临床肿瘤诊疗方向。
细胞焦亡（pyroptosis）是新近发现的一种依赖炎性半胱天冬酶（caspase）的促炎程序性细胞死亡方式（regulated cell death，RCD），主要通过gasdermin家族成员发生剪切活化，引起细胞膜穿孔和细胞内容物释放的过程。Gasdermin E(GSDME)是gasdermin家族的主要成员之一，近来研究发现在几种常见的肿瘤中常因其启动子甲基化而低表达，进而增强了肿瘤的增殖和转移能力；分析其结构和功能显示，GSDME可被激活态的caspase-3切割并形成具有造孔活性的GSDME-N末端结构域，从而诱导肿瘤细胞发生焦亡，介导肿瘤细胞死亡。本文就GSDME介导焦亡的机制及其与肿瘤发生发展的关系作一综述，以期提出新的临床肿瘤诊疗方向。
2021, 28(3):294-298.
DOI: 10.3872/j.issn.1007-385X.2021.03.012
Abstract:
脯氨酰4-羟化酶α亚基(prolyl 4-hydroxylase subunit alpha，P4HA)是胶原蛋白翻译后加工的关键酶，可通过影响胶原蛋白的结构、功能及稳定性诱导肿瘤微环境重塑，从而调节肿瘤细胞极性、运动和信号转导，其与多种实体肿瘤的侵袭、转移密切相关。此外，P4HA可调控肿瘤相关基因表达、增强肿瘤细胞恶性表型表达及耐药性形成，P4HA的失调在肿瘤的生长、侵袭以及治疗抵抗中起重要作用。本文通过概述P4HA的生物学结构、功能及其在实体肿瘤发生发展中的作用机制，对P4HA与肿瘤发生、转移及耐药性关系的研究进展加以阐述。
脯氨酰4-羟化酶α亚基(prolyl 4-hydroxylase subunit alpha，P4HA)是胶原蛋白翻译后加工的关键酶，可通过影响胶原蛋白的结构、功能及稳定性诱导肿瘤微环境重塑，从而调节肿瘤细胞极性、运动和信号转导，其与多种实体肿瘤的侵袭、转移密切相关。此外，P4HA可调控肿瘤相关基因表达、增强肿瘤细胞恶性表型表达及耐药性形成，P4HA的失调在肿瘤的生长、侵袭以及治疗抵抗中起重要作用。本文通过概述P4HA的生物学结构、功能及其在实体肿瘤发生发展中的作用机制，对P4HA与肿瘤发生、转移及耐药性关系的研究进展加以阐述。
2021, 28(3):299-305.
DOI: 10.3872/j.issn.1007-385X.2021.03.013
Abstract:
由抑癌基因 TP53 编码的 p53 是体内最重要的抑癌因子之一。MDM2/MDM4 是 p53 的负向调控因子 ，通过p53-MDM2/MDM4负反馈环路调控p53功能。几乎所有肿瘤均存在p53异常，主要包括p53突变和MDM2/MDM4扩增引起的p53失活。p53相关药物研发一直是肿瘤研究中的热点，然而，直到最近10年才研发出相对成熟的药物。目前，以逆转p53失活为目标的药物研发存在以下几种设计思路：（1）诱导突变p53恢复野生型功能，如PRIMA-1/PRIMA-1MET、COTI-2；（2）促进突变p53降解，如Ganetespib、伏立诺他；（3）阻断MDM2/MDM4，如RG7388、ALRN-6924等。上述药物均已进入临床试验，其中伏立诺他、PRIMA-1MET和ALRN-6924已分别在卵巢癌及骨髓增生异常综合征、皮肤T细胞淋巴瘤、急性髓系白血病中取得较好的疗效。进一步阐明p53-MDM2/MDM4环路异常在肿瘤中的作用机制，对于未来研发p53相关抗肿瘤药物以及指导临床用药具有重要意义。
由抑癌基因 TP53 编码的 p53 是体内最重要的抑癌因子之一。MDM2/MDM4 是 p53 的负向调控因子 ，通过p53-MDM2/MDM4负反馈环路调控p53功能。几乎所有肿瘤均存在p53异常，主要包括p53突变和MDM2/MDM4扩增引起的p53失活。p53相关药物研发一直是肿瘤研究中的热点，然而，直到最近10年才研发出相对成熟的药物。目前，以逆转p53失活为目标的药物研发存在以下几种设计思路：（1）诱导突变p53恢复野生型功能，如PRIMA-1/PRIMA-1MET、COTI-2；（2）促进突变p53降解，如Ganetespib、伏立诺他；（3）阻断MDM2/MDM4，如RG7388、ALRN-6924等。上述药物均已进入临床试验，其中伏立诺他、PRIMA-1MET和ALRN-6924已分别在卵巢癌及骨髓增生异常综合征、皮肤T细胞淋巴瘤、急性髓系白血病中取得较好的疗效。进一步阐明p53-MDM2/MDM4环路异常在肿瘤中的作用机制，对于未来研发p53相关抗肿瘤药物以及指导临床用药具有重要意义。
2021, 28(3):306-310.
DOI: 10.3872/j.issn.1007-385X.2021.03.014
Abstract:
黏膜免疫紊乱促进恶性肿瘤发病的作用日益得到重视。菌群，尤其是肠道菌群，可通过局部效应和“肠肺轴”、“脑肠轴”等远端效应调控黏膜免疫，在恶性肿瘤预防及免疫治疗中发挥重要作用。维护机体菌群和黏膜免疫的平衡有望突破恶性肿瘤整体疗效提高的瓶颈，促进恶性肿瘤整体防控效率的提高。本文对菌群与黏膜免疫的关系及其在防治恶性肿瘤中的近期研究进展加以综述。
黏膜免疫紊乱促进恶性肿瘤发病的作用日益得到重视。菌群，尤其是肠道菌群，可通过局部效应和“肠肺轴”、“脑肠轴”等远端效应调控黏膜免疫，在恶性肿瘤预防及免疫治疗中发挥重要作用。维护机体菌群和黏膜免疫的平衡有望突破恶性肿瘤整体疗效提高的瓶颈，促进恶性肿瘤整体防控效率的提高。本文对菌群与黏膜免疫的关系及其在防治恶性肿瘤中的近期研究进展加以综述。
2021, 28(3):311-316.
DOI: 10.3872/j.issn.1007-385X.2021.03.015
Abstract:
恶性黑色素瘤(malignant melanoma)是恶性程度极高的皮肤恶性肿瘤，其多数发生淋巴结或血液远处转移，转移性恶性黑色素患者5年生存率仅5%～10%，转移是恶性黑色素瘤患者存活率低的重要原因。长链非编码RNA（long non-coding RNA，lncRNA）是不具备蛋白质编码功能且长度普遍大于200个核苷酸的RNA分子，lncRNA差异性表达可能通过调节上皮-间质转化(EMT)相关因素、改变细胞外基质（ECM）性能等环节促进或抑制恶性黑色素瘤的增殖、侵袭和转移过程。本文综述了lncRNA在恶性黑色素瘤侵袭和转移中作用的研究进展，旨在为恶性黑色素瘤转移的早期诊断及预后预测寻找新的标志物。
恶性黑色素瘤(malignant melanoma)是恶性程度极高的皮肤恶性肿瘤，其多数发生淋巴结或血液远处转移，转移性恶性黑色素患者5年生存率仅5%～10%，转移是恶性黑色素瘤患者存活率低的重要原因。长链非编码RNA（long non-coding RNA，lncRNA）是不具备蛋白质编码功能且长度普遍大于200个核苷酸的RNA分子，lncRNA差异性表达可能通过调节上皮-间质转化(EMT)相关因素、改变细胞外基质（ECM）性能等环节促进或抑制恶性黑色素瘤的增殖、侵袭和转移过程。本文综述了lncRNA在恶性黑色素瘤侵袭和转移中作用的研究进展，旨在为恶性黑色素瘤转移的早期诊断及预后预测寻找新的标志物。
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.