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Volume 24,Issue 5,2017 Table of Contents
2017, 24(5):461-466.
DOI: 10.3872/j.issn.1007-385X.2017.05.001
Abstract:
hard to reach the tumor positions and to improve their immunosuppressive microenvironment. When the CAR-T cells eliminate tumor cells, at the same time they also kill normal cells with the same target points. Efficacy of the CAR-T cells therapy for hematologic tumors and solid tumors except B cell tumors still needs to be improved. This paper focuses on that how the CAR-T cells could accurately identify tumor cells via optimization of the CAR-T cell structures and that effectiveness of the CAR-T cell therapy for malignant tumors could be enhanced through overcoming immunosuppressive microenvironment of tumors. At the same time, the CAR-T cells could be better controlled and safety of the CAR-T cells higher.
hard to reach the tumor positions and to improve their immunosuppressive microenvironment. When the CAR-T cells eliminate tumor cells, at the same time they also kill normal cells with the same target points. Efficacy of the CAR-T cells therapy for hematologic tumors and solid tumors except B cell tumors still needs to be improved. This paper focuses on that how the CAR-T cells could accurately identify tumor cells via optimization of the CAR-T cell structures and that effectiveness of the CAR-T cell therapy for malignant tumors could be enhanced through overcoming immunosuppressive microenvironment of tumors. At the same time, the CAR-T cells could be better controlled and safety of the CAR-T cells higher.
2017, 24(5):467-471.
DOI: 10.3872/j.issn.1007-385X.2017.05.002
Abstract:
Objective:To investigate the mechanism of coding gene of cell cyclin D1(CCND1) participating in miR-340-induced inhibition of chemotherapy resistance of colorectal cancer cells to 5-fluorouracil (5-Fu). Methods: Colorectal cancer HCT115 and SW480 cell lines were transfected with si-CCND1and miR340-mimic respectively by transient transfection technology. The sensitivity of cancer cells to 5-Fu after transfection was observed with MTT. The effect of CCND1 on miR-340 mediated suppression of chemotherapy resistance of cancer cells to 5-Fu was validated by double luciferase test. Results: After transient transfection with siCCND1 or over-expression of miR-340, the IC50 values of HCT116 and SW480 cell lines were significantly lower than that of control group \[CCND1 silencing: 10, 10 vs 20 μmol/L; miR-340 over-expressing: 20, 20 vs 40 μmol/L; all P<0.05). After co-transfection with CCND1 3′UTR wild plasmid and miR-340 inhibitor, the luciferase reporter activity in HCT 116 and SW480 cells were significantly higher than that of empty plasmid transfection group or mimic transfection group (P<0.01). Conclusion: CCND1, as an unfavorable factor, enhances the chemo-resistance of colorectal cancer cells to 5-FU by inhibiting the expression of miR-340.
Objective:To investigate the mechanism of coding gene of cell cyclin D1(CCND1) participating in miR-340-induced inhibition of chemotherapy resistance of colorectal cancer cells to 5-fluorouracil (5-Fu). Methods: Colorectal cancer HCT115 and SW480 cell lines were transfected with si-CCND1and miR340-mimic respectively by transient transfection technology. The sensitivity of cancer cells to 5-Fu after transfection was observed with MTT. The effect of CCND1 on miR-340 mediated suppression of chemotherapy resistance of cancer cells to 5-Fu was validated by double luciferase test. Results: After transient transfection with siCCND1 or over-expression of miR-340, the IC50 values of HCT116 and SW480 cell lines were significantly lower than that of control group \[CCND1 silencing: 10, 10 vs 20 μmol/L; miR-340 over-expressing: 20, 20 vs 40 μmol/L; all P<0.05). After co-transfection with CCND1 3′UTR wild plasmid and miR-340 inhibitor, the luciferase reporter activity in HCT 116 and SW480 cells were significantly higher than that of empty plasmid transfection group or mimic transfection group (P<0.01). Conclusion: CCND1, as an unfavorable factor, enhances the chemo-resistance of colorectal cancer cells to 5-FU by inhibiting the expression of miR-340.
LIU Chao
,
WANG Jiwei
,
WANG Pengju
,
ZHANG Zhongxian
,
CHU Yongchao
,
LYU Pengwei
,
GU Yuanting
,
WANG Yaohe
2017, 24(5):472-477.
DOI: 10.3872/j.issn.1007-385X.2017.05.003
Abstract:
Objective:To evaluate the in vitro and in vivo efficacy of tumor-targeted oncolytic vaccinia virus (VV) vectors, VVΔTKΔN1L-RFP and VVΔTKΔN1L-mIL-21, on murine breast cancer cell lines (JC, TUBO and 4T1).Methods: The cytotoxicity of the viruses (VVΔTKΔN1L-RFP and VVΔTKΔN1L-mIL-21) at different mass concentrations on JC, TUBO and 4T1 cells was compared by MTT assay. The replication ability of the two viruses in the three cell lines was tested by TCID50. ELISA assay was performed to detect mIL-21 expression in the supernatants of the culture medium of three cell lines after virus infection. Orthotopic models of triple negative breast cancer (4T1) and Her-2 amplified breast cancer (TUBO) in the BALB/c mice were established to investigate the antitumor efficacy of the two VVs. Results:The two viruses were all able to replicate in breast cancer JC, TUBO and 4T1 cell lines, and low dose of VV caused significant cytotoxicity against breast cancer cell lines. High level of mIL-21 protein was detected in the cell culture supernatants after VVΔTKΔN1L-mIL-21 infection. In the orthotopic 4T1 breast cancer model, the viruses did not show significant anti-tumor effect (P>0.05); however, in the orthotopic TUBO breast cancer model, tumor growth was significantly inhibited by both viruses (P<0.05，P<0.01), and the survival time（P<0.01) of tumor bearing mouse was prolonged in both VVΔTKΔN1L-RFP and VVΔTKΔN1L-mIL-21 treatment group. Conclusion: Both VVΔTKΔN1L-RFP and VVΔTKΔN1L-mIL-21viruses could specifically replicate and showed cell killing effect on breast cancer cells. The two viruses have different in vivo therapeutic effects on Her-2 gene amplified breast cancer and triple negative breast cancer.
Objective:To evaluate the in vitro and in vivo efficacy of tumor-targeted oncolytic vaccinia virus (VV) vectors, VVΔTKΔN1L-RFP and VVΔTKΔN1L-mIL-21, on murine breast cancer cell lines (JC, TUBO and 4T1).Methods: The cytotoxicity of the viruses (VVΔTKΔN1L-RFP and VVΔTKΔN1L-mIL-21) at different mass concentrations on JC, TUBO and 4T1 cells was compared by MTT assay. The replication ability of the two viruses in the three cell lines was tested by TCID50. ELISA assay was performed to detect mIL-21 expression in the supernatants of the culture medium of three cell lines after virus infection. Orthotopic models of triple negative breast cancer (4T1) and Her-2 amplified breast cancer (TUBO) in the BALB/c mice were established to investigate the antitumor efficacy of the two VVs. Results:The two viruses were all able to replicate in breast cancer JC, TUBO and 4T1 cell lines, and low dose of VV caused significant cytotoxicity against breast cancer cell lines. High level of mIL-21 protein was detected in the cell culture supernatants after VVΔTKΔN1L-mIL-21 infection. In the orthotopic 4T1 breast cancer model, the viruses did not show significant anti-tumor effect (P>0.05); however, in the orthotopic TUBO breast cancer model, tumor growth was significantly inhibited by both viruses (P<0.05，P<0.01), and the survival time（P<0.01) of tumor bearing mouse was prolonged in both VVΔTKΔN1L-RFP and VVΔTKΔN1L-mIL-21 treatment group. Conclusion: Both VVΔTKΔN1L-RFP and VVΔTKΔN1L-mIL-21viruses could specifically replicate and showed cell killing effect on breast cancer cells. The two viruses have different in vivo therapeutic effects on Her-2 gene amplified breast cancer and triple negative breast cancer.
2017, 24(5):478-483.
DOI: 10.3872/j.issn.1007-385X.2017.05.004
Abstract:
Objective:To investigate effect of crosslinked CD44 molecule on expression of Fas in the human mast cell leukemia HMC-1 cell line and its mediated-apoptosis of the cell. Methods: Using flow cytometry assay, expressions of the CD44 and Fas on surface of the HMC-1 cell were detected, and changes of Fas expression on the cell surface after treatment with native hyaluronan (HA) and crosslinking the CD44 molecule with anti-CD44 antibody were observed, and then effects of PKC inhibitor (H-7), PI3K inhibitor (wortmannin), inhibitors of MAPK signaling pathway, inhibitor of protein synthesis (CHX) and inhibitor of actin polymerization (cytochalasin B, CB) on expression of Fas on the surface of the cells with the crosslinked CD44 were tested. Effect of the crosslinked CD44 on expression of Fas mRNA was detected by Northern hybridization assay. With Annexin V/PI double staining, effect of the crosslinked CD44, HA or F-HA on Fas-mediated cell apoptosis was examined. Results: In the HMC-1 cell, expression of the CD44 was high and expression of Fas was low. The crosslinked CD44 molecule significantly enhanced expression of Fas on the cell surface (P<0.05), but transcription level of Fas mRNA did not obviously changed. Inhibitor of actin polymerization (CB) could inhibit up-regulation of Fas expression by the CD44 (P<0.05). Inhibitors of cell signaling pathway and protein synthesis which were detected couldn’t inhibit up-regulation of Fas expression (P<0.05). All of F-HA and the crosslinked CD44 could promote Fas-mediated cell apoptosis. Conclusion: The crossliking of CD44 up-regulates Fas expression in the HMC-1 cell, and enhances Fas-mediated cell apoptosis. The CD44 molecule could become a novel target for treatment of the mast cell leukemia.
Objective:To investigate effect of crosslinked CD44 molecule on expression of Fas in the human mast cell leukemia HMC-1 cell line and its mediated-apoptosis of the cell. Methods: Using flow cytometry assay, expressions of the CD44 and Fas on surface of the HMC-1 cell were detected, and changes of Fas expression on the cell surface after treatment with native hyaluronan (HA) and crosslinking the CD44 molecule with anti-CD44 antibody were observed, and then effects of PKC inhibitor (H-7), PI3K inhibitor (wortmannin), inhibitors of MAPK signaling pathway, inhibitor of protein synthesis (CHX) and inhibitor of actin polymerization (cytochalasin B, CB) on expression of Fas on the surface of the cells with the crosslinked CD44 were tested. Effect of the crosslinked CD44 on expression of Fas mRNA was detected by Northern hybridization assay. With Annexin V/PI double staining, effect of the crosslinked CD44, HA or F-HA on Fas-mediated cell apoptosis was examined. Results: In the HMC-1 cell, expression of the CD44 was high and expression of Fas was low. The crosslinked CD44 molecule significantly enhanced expression of Fas on the cell surface (P<0.05), but transcription level of Fas mRNA did not obviously changed. Inhibitor of actin polymerization (CB) could inhibit up-regulation of Fas expression by the CD44 (P<0.05). Inhibitors of cell signaling pathway and protein synthesis which were detected couldn’t inhibit up-regulation of Fas expression (P<0.05). All of F-HA and the crosslinked CD44 could promote Fas-mediated cell apoptosis. Conclusion: The crossliking of CD44 up-regulates Fas expression in the HMC-1 cell, and enhances Fas-mediated cell apoptosis. The CD44 molecule could become a novel target for treatment of the mast cell leukemia.
2017, 24(5):484-489.
DOI: 10.3872/j.issn.1007-385X.2017.05.005
Abstract:
Objective:To explore the influence of CHD1L gene (chromodomain helicase/ATPase DNA binding protein 1-like gene) on the invasion and migration ability of prostate cancer cells and the potential mechanisms. Methods: Real-time fluorescent quantitative-PCR assay was carried out to detect mRNA expression of CHD1L gene in prostate cancer cell lines LNCAP, PC3 and DU 145 as well as normal prostate epithelial cell line RWPE-1. siRNA transfection was used to deplete CHD1L expression in PC3 cells. Then Transwell invasion assay and wound healing test were employed to detect the effect of CHD1Lsilencing on the invasion and migration ability of PC3 cells. Protein expressions of MMP-9, N-cadherin and E-cadherin were examined by Western blotting assay. Results: Compared to normal prostate epithelial cells, three prostate cancer cell lines all showed significantly higher expression of CHD1L mRNA (P<0.01), and PC3 cells demonstrated the highest CHD1LmRNA expression. Invasion assay showed that the trans-membrane cell number in CHD1L silencing group was significantly lower than that in negative and blank control groups (49.67±6.67 vs 113.67±5.69 and 112.00±12.49, P<0.05). Wound healing test also exhibited lower healing degree in CHD1L silencing group than that in negative and blank control groups at 48 h (\[21.27±3.27\]% vs \[48.47±5.72\]% and \[49.93±3.35\]%, respectively, P<0.05). Furthermore, protein expressions of MMP-9 and N-cadherin decreased while E-cadherin increased in CHD1L gene depletion cells. Conclusions: CHD1L silencing could dampen the invasion and migration ability of prostate cancer PC3 cell line, and this might be accomplished by regulating MMP-9 and EMT related proteins.
Objective:To explore the influence of CHD1L gene (chromodomain helicase/ATPase DNA binding protein 1-like gene) on the invasion and migration ability of prostate cancer cells and the potential mechanisms. Methods: Real-time fluorescent quantitative-PCR assay was carried out to detect mRNA expression of CHD1L gene in prostate cancer cell lines LNCAP, PC3 and DU 145 as well as normal prostate epithelial cell line RWPE-1. siRNA transfection was used to deplete CHD1L expression in PC3 cells. Then Transwell invasion assay and wound healing test were employed to detect the effect of CHD1Lsilencing on the invasion and migration ability of PC3 cells. Protein expressions of MMP-9, N-cadherin and E-cadherin were examined by Western blotting assay. Results: Compared to normal prostate epithelial cells, three prostate cancer cell lines all showed significantly higher expression of CHD1L mRNA (P<0.01), and PC3 cells demonstrated the highest CHD1LmRNA expression. Invasion assay showed that the trans-membrane cell number in CHD1L silencing group was significantly lower than that in negative and blank control groups (49.67±6.67 vs 113.67±5.69 and 112.00±12.49, P<0.05). Wound healing test also exhibited lower healing degree in CHD1L silencing group than that in negative and blank control groups at 48 h (\[21.27±3.27\]% vs \[48.47±5.72\]% and \[49.93±3.35\]%, respectively, P<0.05). Furthermore, protein expressions of MMP-9 and N-cadherin decreased while E-cadherin increased in CHD1L gene depletion cells. Conclusions: CHD1L silencing could dampen the invasion and migration ability of prostate cancer PC3 cell line, and this might be accomplished by regulating MMP-9 and EMT related proteins.
6 Effects of EZH2 and H3K27me3 expression on migration and invasion of esophageal carcinoma cells
2017, 24(5):490-496.
DOI: 10.3872/j.issn.1007-385X.2017.05.006
Abstract:
Objective:To study the effect of enhancer of zeste homolog 2(EZH2) and histone H3 methylated Lys27 (H3K27me3) on the migration and invasion ability of esophageal squamous cell cancer (ESCC) cells by transfection of vectors expressing/knock down EZH2. Methods: Quantificational real-time PCR(qRT-PCR) and Western blotting were performed to evaluate the expression levels of EZH2in esophageal carcinoma cell lines (KYSE30, KYSE170, TE1, Eca109), as well as the effect of over-expression or knockdown of EZH2 on H3K27me3 expression in ESCC cell lines. Effect of EZH2 over-expression or knockdown on migration and invasion abilities of ESCC cells were examined by wound healing assay and Transwell invasion test, respectively. The expression level of MMPs in ESCC cells after over-expression or knockdown of EZH2 were detected by qRT-PCR.Results: The expressions of EZH2 and H3K27me3 in Eca109 and TE1 cells were significantly higher than those in KYSE30 and KYSE170 cells (P<0.05). Over-expression of EZH2 promoted the expression of H3K27me3 in KYSE30 and KYSE170 cell lines (P<0.05). Knockdown of EZH2inhibited the expression of H3K27me3 in Eca109 and TE1 cell lines (P<0.05). The trans-membrane number of KYSE30 and KYSE170 cells was significantly increased (\[281.33±4.10\] vs \[132.00±4.00\], P<0.05; \[241.67±4.04\] vs \[105.33±3.51\], P<0.05), and the migration distance of KYSE30 and KYSE170 cells was significantly increased (\[63.6±1.2\] vs \[23.0±2.3\] μm, P<0.05; \[62.5±2.5\] vs \[21.2±1.0\] μm, P<0.05) after over-expression of EZH2. Knockdown of EZH2significantly decreased the trans-membrane number of Eca109 and TE1 cells (all P<0.05), and the migration distance was also decreased after transfection with shEZH2 (all P<0.05). Conclusion: EZH2 can enhance trimethylation of lysine 27 on histone H3 (H3K27) of the target gene promoters, and promote the migration and invasion abilities of esophageal carcinoma cell lines.
Objective:To study the effect of enhancer of zeste homolog 2(EZH2) and histone H3 methylated Lys27 (H3K27me3) on the migration and invasion ability of esophageal squamous cell cancer (ESCC) cells by transfection of vectors expressing/knock down EZH2. Methods: Quantificational real-time PCR(qRT-PCR) and Western blotting were performed to evaluate the expression levels of EZH2in esophageal carcinoma cell lines (KYSE30, KYSE170, TE1, Eca109), as well as the effect of over-expression or knockdown of EZH2 on H3K27me3 expression in ESCC cell lines. Effect of EZH2 over-expression or knockdown on migration and invasion abilities of ESCC cells were examined by wound healing assay and Transwell invasion test, respectively. The expression level of MMPs in ESCC cells after over-expression or knockdown of EZH2 were detected by qRT-PCR.Results: The expressions of EZH2 and H3K27me3 in Eca109 and TE1 cells were significantly higher than those in KYSE30 and KYSE170 cells (P<0.05). Over-expression of EZH2 promoted the expression of H3K27me3 in KYSE30 and KYSE170 cell lines (P<0.05). Knockdown of EZH2inhibited the expression of H3K27me3 in Eca109 and TE1 cell lines (P<0.05). The trans-membrane number of KYSE30 and KYSE170 cells was significantly increased (\[281.33±4.10\] vs \[132.00±4.00\], P<0.05; \[241.67±4.04\] vs \[105.33±3.51\], P<0.05), and the migration distance of KYSE30 and KYSE170 cells was significantly increased (\[63.6±1.2\] vs \[23.0±2.3\] μm, P<0.05; \[62.5±2.5\] vs \[21.2±1.0\] μm, P<0.05) after over-expression of EZH2. Knockdown of EZH2significantly decreased the trans-membrane number of Eca109 and TE1 cells (all P<0.05), and the migration distance was also decreased after transfection with shEZH2 (all P<0.05). Conclusion: EZH2 can enhance trimethylation of lysine 27 on histone H3 (H3K27) of the target gene promoters, and promote the migration and invasion abilities of esophageal carcinoma cell lines.
2017, 24(5):497-502.
DOI: 10.3872/j.issn.1007-385X.2017.05.007
Abstract:
Objective:To investigate the expression of lncRNA HOXA11-AS in osteosarcoma, and to explore its effect on proliferation, migration and invasion of osteosarcoma cells and the possible mechanism. Methods:Thirteen cases of osteosarcoma tissues and corresponding adjacent normal tissues were collected from the Department of Bone Surgery, the People’s Hospital of Zhejiang Province during January 2012 to December 2015. Osteosarcoma cell MG63, U205 lines and human osteoblast cell hFOB1.19 line were used. Real-time fluorescent quantitative PCR was performed to detect the lncRNA HOXA11-AS expression in osteosarcoma specimens and osteosarcoma MG63 and U20S cell lines. Lentiviral vectors that stably over-expressing lncRNA HOXA11-AS were constructed and transfected into MG63 and U20S cell lines; CCK8 assay and colony-formation assay were performed to investigate the effect of lncRNA HOXA11-AS on osteosarcoma cell proliferation; Transwell assay was performed to investigate the effect of lncRNA HOXA11-AS on migration and invasion of osteosarcoma cells. Nude mice model of MG63 osteosarcoma xenograft, which over-expressing lncRNA HOXA11-AS, was established to observe the effect of lncRNA HOXA11-AS on xenograft growth in mice, by comparing with Lv-NC transfected cell xenografts. Results: lncRNA HOXA11-AS was markedly down-regulated in tumor tissues and osteosarcoma cell lines (P<0.01). Over-expression of lncRNA HOXA11-AS significantly suppressed (1) the proliferation, migration and invasion of U20S and MG63 cells (proliferation: \[4.03±0.98\] times vs \[6.96±0.54\] times, \[4.68±0.77\] times vs \[8.87±1.23\] times, all P<0.01; migration: \[83.00±6.03\] vs \[168±12.54\], \[96±8.77\] vs \[184±14.63\], all P<0.01; invasion: \[35.00±3.48\] vs \[97.00±8.32\], \[38.00±1.73\] vs \[87.00±6.37\], all P＜0.01); (2) the growth of xenografts in rats（P<0.01）. Conclusion:lncRNA HOXA11-AS significantly down-regulated in osteosarcoma cells, and suppressed the progression of osteosarcoma. lncRNA HOXA11-AS can be served as a therapeutic target for osteosarcoma.
Objective:To investigate the expression of lncRNA HOXA11-AS in osteosarcoma, and to explore its effect on proliferation, migration and invasion of osteosarcoma cells and the possible mechanism. Methods:Thirteen cases of osteosarcoma tissues and corresponding adjacent normal tissues were collected from the Department of Bone Surgery, the People’s Hospital of Zhejiang Province during January 2012 to December 2015. Osteosarcoma cell MG63, U205 lines and human osteoblast cell hFOB1.19 line were used. Real-time fluorescent quantitative PCR was performed to detect the lncRNA HOXA11-AS expression in osteosarcoma specimens and osteosarcoma MG63 and U20S cell lines. Lentiviral vectors that stably over-expressing lncRNA HOXA11-AS were constructed and transfected into MG63 and U20S cell lines; CCK8 assay and colony-formation assay were performed to investigate the effect of lncRNA HOXA11-AS on osteosarcoma cell proliferation; Transwell assay was performed to investigate the effect of lncRNA HOXA11-AS on migration and invasion of osteosarcoma cells. Nude mice model of MG63 osteosarcoma xenograft, which over-expressing lncRNA HOXA11-AS, was established to observe the effect of lncRNA HOXA11-AS on xenograft growth in mice, by comparing with Lv-NC transfected cell xenografts. Results: lncRNA HOXA11-AS was markedly down-regulated in tumor tissues and osteosarcoma cell lines (P<0.01). Over-expression of lncRNA HOXA11-AS significantly suppressed (1) the proliferation, migration and invasion of U20S and MG63 cells (proliferation: \[4.03±0.98\] times vs \[6.96±0.54\] times, \[4.68±0.77\] times vs \[8.87±1.23\] times, all P<0.01; migration: \[83.00±6.03\] vs \[168±12.54\], \[96±8.77\] vs \[184±14.63\], all P<0.01; invasion: \[35.00±3.48\] vs \[97.00±8.32\], \[38.00±1.73\] vs \[87.00±6.37\], all P＜0.01); (2) the growth of xenografts in rats（P<0.01）. Conclusion:lncRNA HOXA11-AS significantly down-regulated in osteosarcoma cells, and suppressed the progression of osteosarcoma. lncRNA HOXA11-AS can be served as a therapeutic target for osteosarcoma.
2017, 24(5):503-509.
DOI: 10.3872/j.issn.1007-385X.2017.05.008
Abstract:
Objective:To explore the effect of human placenta extracts (HPE) on the proliferation and migration of human colon cancer cell lines (Caco-2 and SW480). Methods: Human colon cancer Caco-2 and SW480 cell lines were treated with different concentrations of HPE. Cell proliferation was determined by CCK-8, Ki-67 and CFSE dilution. The effect of HPE on cell apoptosis and cell cycle were detected by Annexin-V/PI and DAPI staining. The expressions of apoptosis related gene BAX, CDK2and CyclinA2 were determined by Real-time PCR. The migration efficiency of cell was measured by wound-healing assay. Human colon cancer cells were subcutaneously injected into the nude mice to establish xenograft model, and the mice were randomly divided into different groups and given different treatments of HPE and/or 5-fluorouracil (5-Fu). The tumor volume and body weight were recorded. Results: The cell proliferation ability of both Caco-2 and SW480 cells cultured with HPE was lower than that of control group (0.82± 0.01 vs 0.96±0.02, P<001; 0.90±0.03 vs 0.96±0.02, P<0.05); and the apoptotic rates in HPE treatment group were significantly higher than control group (\[20.47±1.32\]% vs \[11.01±3.82\]%, P<0.01; \[20.70±5.19\]% vs \[8.00±2.69\]%, P<005) , accompanied with cytoplasmic reduction, nuclear pyknosis and increased BAX gene expression (3.23±1.90 vs 1.00±0.00; 2.25±0.55 vs 1.00±0.00, all P<0.05). Furthermore, S-phase arrest with an apoptosis peak was observed in HPE treatment group, and decreased mRNA expressions of CDK2 and CyclinA2 (all P<0.05) in Caco-2 cells were also observed. Moreover, an obvious lower wound-healing rate was identified in cells treated with HPE (\[0.17±029\] vs \[1.50±0.50\] mm, P<0.05). The tumor volume of mice in HPE-treated group was smaller than that of control group, and higher survival rate was observed than that of 5-Fu alone group. Conclusion: This study indicated that HPE could inhibit the proliferation and migration ability of human colon cancer cells both in vitro and in vivo, partly through enhancing cell apoptosis and S-phase arrest, which may contribute to the inhibition on growth of certain tumor cells.
Objective:To explore the effect of human placenta extracts (HPE) on the proliferation and migration of human colon cancer cell lines (Caco-2 and SW480). Methods: Human colon cancer Caco-2 and SW480 cell lines were treated with different concentrations of HPE. Cell proliferation was determined by CCK-8, Ki-67 and CFSE dilution. The effect of HPE on cell apoptosis and cell cycle were detected by Annexin-V/PI and DAPI staining. The expressions of apoptosis related gene BAX, CDK2and CyclinA2 were determined by Real-time PCR. The migration efficiency of cell was measured by wound-healing assay. Human colon cancer cells were subcutaneously injected into the nude mice to establish xenograft model, and the mice were randomly divided into different groups and given different treatments of HPE and/or 5-fluorouracil (5-Fu). The tumor volume and body weight were recorded. Results: The cell proliferation ability of both Caco-2 and SW480 cells cultured with HPE was lower than that of control group (0.82± 0.01 vs 0.96±0.02, P<001; 0.90±0.03 vs 0.96±0.02, P<0.05); and the apoptotic rates in HPE treatment group were significantly higher than control group (\[20.47±1.32\]% vs \[11.01±3.82\]%, P<0.01; \[20.70±5.19\]% vs \[8.00±2.69\]%, P<005) , accompanied with cytoplasmic reduction, nuclear pyknosis and increased BAX gene expression (3.23±1.90 vs 1.00±0.00; 2.25±0.55 vs 1.00±0.00, all P<0.05). Furthermore, S-phase arrest with an apoptosis peak was observed in HPE treatment group, and decreased mRNA expressions of CDK2 and CyclinA2 (all P<0.05) in Caco-2 cells were also observed. Moreover, an obvious lower wound-healing rate was identified in cells treated with HPE (\[0.17±029\] vs \[1.50±0.50\] mm, P<0.05). The tumor volume of mice in HPE-treated group was smaller than that of control group, and higher survival rate was observed than that of 5-Fu alone group. Conclusion: This study indicated that HPE could inhibit the proliferation and migration ability of human colon cancer cells both in vitro and in vivo, partly through enhancing cell apoptosis and S-phase arrest, which may contribute to the inhibition on growth of certain tumor cells.
2017, 24(5):510-515.
DOI: 10.3872/j.issn.1007-385X.2017.05.009
Abstract:
Objective: To investigate the effects of recombinant Newcastle disease virus (rNDV) expressing IL-29（rNDV IL-29）on the proliferation, migration and apoptosis of lung adenocarcinoma A549 cells. Methods: A549 cells were treated with rNDV IL-29, NDV and PBS respectively, namely rNDV IL-29 group, NDV group and control group. The protein and gene expression of IL-29 in A549 cells were examined by RT-PCR, immunofluorescence and Western blotting; MTT assay, colony formation assay and scratch assay were used to evaluate the effect of rNDV IL-29 on proliferation and migration ability of A549 cells; Flow cytometry and Western blotting were used to examine the effect of rNDV IL-29 on apoptosis of A549 cells. Results:Compared with NDV group and control group, (1) IL-29 protein and gene expressions were dramatically increased in rNDV IL-29 group. (2) the rate of cell proliferation in rNDV IL-29 group was significantly inhibited (\[56.48±11.89\]% vs \[42.18±6.18\]%, P<0.05), and migration ability of A549 cells in rNDV IL-29 group was statistically decreased (\[5.00±4.00\]% vs \[32.43±3.71\]%, \[84.57±3.96\]%, all P<0.05). (3) the expression of caspase3 in rNDV IL-29 group was significantly up-regulated (\[29.67±1.53\]% vs \[18.33±3.06\]%, \[7.0±6.08\]%, all P<0.05), while Bcl-2/bax level was remarkably reduced (\[12.00±2.65\]% vs \[42.33±586\]%, \[67.00±6.25\]%, all P<0.05\]. Conclusion: rNDV IL-29 inhibits the proliferation and migration of A549 cells and promotes apoptosis of A549, suggesting that rNDV IL-29 may be served as a potential anticancer drug.
Objective: To investigate the effects of recombinant Newcastle disease virus (rNDV) expressing IL-29（rNDV IL-29）on the proliferation, migration and apoptosis of lung adenocarcinoma A549 cells. Methods: A549 cells were treated with rNDV IL-29, NDV and PBS respectively, namely rNDV IL-29 group, NDV group and control group. The protein and gene expression of IL-29 in A549 cells were examined by RT-PCR, immunofluorescence and Western blotting; MTT assay, colony formation assay and scratch assay were used to evaluate the effect of rNDV IL-29 on proliferation and migration ability of A549 cells; Flow cytometry and Western blotting were used to examine the effect of rNDV IL-29 on apoptosis of A549 cells. Results:Compared with NDV group and control group, (1) IL-29 protein and gene expressions were dramatically increased in rNDV IL-29 group. (2) the rate of cell proliferation in rNDV IL-29 group was significantly inhibited (\[56.48±11.89\]% vs \[42.18±6.18\]%, P<0.05), and migration ability of A549 cells in rNDV IL-29 group was statistically decreased (\[5.00±4.00\]% vs \[32.43±3.71\]%, \[84.57±3.96\]%, all P<0.05). (3) the expression of caspase3 in rNDV IL-29 group was significantly up-regulated (\[29.67±1.53\]% vs \[18.33±3.06\]%, \[7.0±6.08\]%, all P<0.05), while Bcl-2/bax level was remarkably reduced (\[12.00±2.65\]% vs \[42.33±586\]%, \[67.00±6.25\]%, all P<0.05\]. Conclusion: rNDV IL-29 inhibits the proliferation and migration of A549 cells and promotes apoptosis of A549, suggesting that rNDV IL-29 may be served as a potential anticancer drug.
2017, 24(5):516-520.
DOI: 10.3872/j.issn.1007-385X.2017.05.010
Abstract:
Objective:To explore the effect and mechanism of IL-17A on invasion and migration of colon cancer SW480 cells.Methods: Colon cancer SW480 cells were in vitro cultured and divided into experimental group (IL-17A 50 ng/ml) and control group (blank group). The migration ability was observed by cell scratch assay, the invasion feature of SW480 cells was detected by Transwell assay, and the expressions of MMP-2/9 protein and PI3k/AKT/NF-κ B pathway related proteins were tested by Western blotting. Results: After the treatment with IL-17A(50 ng/ml), (1) the migration distance and trans-membrane number of SW480 cells significantly increased (\[2.49±018\] mm vs \[1.54±0.21\] mm; \[262.00±24.60\] vs \[92.00±31.16\]; all P<0.05); (2) the expression of MMP-2/9 protein in SW480 cells was obviously up-regulated (\[0.41±0.05\] vs \[0.23±0.03\]; \[0.76±0.09\] vs \[0.25±0.04\], all P<0.05); (3) AKT-phosphorylation level in SW480 cells was significantly increased (\[0.72±0.1\] vs \[028±0.04\], P<0.05), and the protein expressions of P65 and P50 were significantly increased (\[0.78±0.10\] vs \[0.35±0.04\]; \[0.85±0.15\] vs \[0.44±0.06\], all P<0.05); however, the protein expressions of c-Rel, ReLB, and P52 showed no significant difference (P>0.05). Conclusion: IL-17A induced the migration and invasion of colon cancer SW480 cells, and increased tumor cell viability; the mechanism may be related to the activation of PI3K/AKT/NF-κB pathway and up-regulation of MMP-2/9 protein expression.
Objective:To explore the effect and mechanism of IL-17A on invasion and migration of colon cancer SW480 cells.Methods: Colon cancer SW480 cells were in vitro cultured and divided into experimental group (IL-17A 50 ng/ml) and control group (blank group). The migration ability was observed by cell scratch assay, the invasion feature of SW480 cells was detected by Transwell assay, and the expressions of MMP-2/9 protein and PI3k/AKT/NF-κ B pathway related proteins were tested by Western blotting. Results: After the treatment with IL-17A(50 ng/ml), (1) the migration distance and trans-membrane number of SW480 cells significantly increased (\[2.49±018\] mm vs \[1.54±0.21\] mm; \[262.00±24.60\] vs \[92.00±31.16\]; all P<0.05); (2) the expression of MMP-2/9 protein in SW480 cells was obviously up-regulated (\[0.41±0.05\] vs \[0.23±0.03\]; \[0.76±0.09\] vs \[0.25±0.04\], all P<0.05); (3) AKT-phosphorylation level in SW480 cells was significantly increased (\[0.72±0.1\] vs \[028±0.04\], P<0.05), and the protein expressions of P65 and P50 were significantly increased (\[0.78±0.10\] vs \[0.35±0.04\]; \[0.85±0.15\] vs \[0.44±0.06\], all P<0.05); however, the protein expressions of c-Rel, ReLB, and P52 showed no significant difference (P>0.05). Conclusion: IL-17A induced the migration and invasion of colon cancer SW480 cells, and increased tumor cell viability; the mechanism may be related to the activation of PI3K/AKT/NF-κB pathway and up-regulation of MMP-2/9 protein expression.
2017, 24(5):521-526.
DOI: 10.3872/j.issn.1007-385X.2017.05.011
Abstract:
Objective:To investigate the effect and mechanism of Klotho gene on the biological characteristics of cervical squamous cell carcinoma SiHa cells. Methods: The expression of Klotho in the cervical squamous cell carcinoma cell SiHa, HeLa and C33A lines and the human immortalized epidermal cell HaCaT line was detected by Real-time PCR and Western blotting. Vectors over-expressing Klotho were constructed and used to transfect SiHa cells, and then the cell proliferation, apoptosis and migration were detected with CCK-8 assay, Flow cytometry and Transwell assay, respectively. The expressions of Rho A and ROCK 1 at protein level were measured with Western blotting assay. Results: Expressions of Klotho in cervical cancer cell SiHa, Hela and C33A lines were lower than that in the HeCaT line (P<0.05). After over-expression of Klotho in SiHa cells, (1) cell proliferation was significantly decreased, compared with control group (\[67.37±5.04\]% vs \[100.34±7.62\]%, P<0.05); (2) the percentage of cells at G0/G1 phrase was increased(\[61.37±3.28\]% vs \[82.56±3.89\]%, P<0.05), while the percentage at S phrase was decreased (\[9.12±248\]% vs \[28.97±2.08\]%, P<0.01); (3) cell apoptotic rate at both early and late stage were all decreased (all P<0.05); (4) cell migration was suppressed (P<0.01); (5) the expressions of Rho A and ROCK 1 at protein level were significantly decreased (all P<0.01). Conclusion: Klotho suppressed SiHa cell proliferation and migration, and promoted cell apoptosis; the mechanism may be related to the suppression of Rho A/ROCK 1 signaling pathway activation, suggesting that Klotho may be used as a potential new target for diagnosis and targeted therapy of cervical squamous cell carcinoma.
Objective:To investigate the effect and mechanism of Klotho gene on the biological characteristics of cervical squamous cell carcinoma SiHa cells. Methods: The expression of Klotho in the cervical squamous cell carcinoma cell SiHa, HeLa and C33A lines and the human immortalized epidermal cell HaCaT line was detected by Real-time PCR and Western blotting. Vectors over-expressing Klotho were constructed and used to transfect SiHa cells, and then the cell proliferation, apoptosis and migration were detected with CCK-8 assay, Flow cytometry and Transwell assay, respectively. The expressions of Rho A and ROCK 1 at protein level were measured with Western blotting assay. Results: Expressions of Klotho in cervical cancer cell SiHa, Hela and C33A lines were lower than that in the HeCaT line (P<0.05). After over-expression of Klotho in SiHa cells, (1) cell proliferation was significantly decreased, compared with control group (\[67.37±5.04\]% vs \[100.34±7.62\]%, P<0.05); (2) the percentage of cells at G0/G1 phrase was increased(\[61.37±3.28\]% vs \[82.56±3.89\]%, P<0.05), while the percentage at S phrase was decreased (\[9.12±248\]% vs \[28.97±2.08\]%, P<0.01); (3) cell apoptotic rate at both early and late stage were all decreased (all P<0.05); (4) cell migration was suppressed (P<0.01); (5) the expressions of Rho A and ROCK 1 at protein level were significantly decreased (all P<0.01). Conclusion: Klotho suppressed SiHa cell proliferation and migration, and promoted cell apoptosis; the mechanism may be related to the suppression of Rho A/ROCK 1 signaling pathway activation, suggesting that Klotho may be used as a potential new target for diagnosis and targeted therapy of cervical squamous cell carcinoma.
2017, 24(5):527-532.
DOI: 10.3872/j.issn.1007-385X.2017.05.012
Abstract:
Objective:Applying solid phase antibody chip against multiple factors to screen serum marker proteins of the patients with lung carcinoma who were treated by immunocytotherapy as clinical diagnosis index and to establish an evaluation model for clinical efficacy of the patients with lung carcinoma.Methods:Using Proteome ProfilerTM solid phase antibody chip against multiple factors and Image J software to analyze gray scale/optical density of the serum marker proteins from 5 patients with advanced lung carcinoma, 5 patients with improved lung carcinoma and 10 healthy individuals. The protein gray values obtained were analyzed by SPSS software, and Fisher model for evaluation of clinical efficacy of the patients with lung carcinoma was established. Results: Analyzing and comparing the common marker proteins among the patients with advanced lung carcinoma, the patients with improved lung carcinoma and the healthy individuals, 8 proteins that are dipeptidyl peptidase Ⅳ, growth hormone, IL-4, myeloperoxidase, osteopontin, receptor of advanced glycation endproducts, TNF-α, and urokinase type plasminogen activator receptor with significant difference (P<0.05) were obtained. Clustering and analyzing data for all of the patients and the healthy individuals in the experiment found that the 8 proteins can very well distinguish the patients with advanced lung carcinoma from the patients with improved lung carcinoma and the healthy individuals. The Fisher model for lung carcinoma was confirmed. Conclusion: The solid phase antibody chip against multiple factors and optimal statistical methods could screen out the serum protein biomarkers related to occurrence, development and efficacy of lung carcinoma, which could establish a certain basis of clinical trail for researches on the mechanism of lung carcinogenesis as well as clinical diagnosis and treatment of the lung carcinoma. It could play an important guiding role in the individualized treatment of the lung carcinoma.
Objective:Applying solid phase antibody chip against multiple factors to screen serum marker proteins of the patients with lung carcinoma who were treated by immunocytotherapy as clinical diagnosis index and to establish an evaluation model for clinical efficacy of the patients with lung carcinoma.Methods:Using Proteome ProfilerTM solid phase antibody chip against multiple factors and Image J software to analyze gray scale/optical density of the serum marker proteins from 5 patients with advanced lung carcinoma, 5 patients with improved lung carcinoma and 10 healthy individuals. The protein gray values obtained were analyzed by SPSS software, and Fisher model for evaluation of clinical efficacy of the patients with lung carcinoma was established. Results: Analyzing and comparing the common marker proteins among the patients with advanced lung carcinoma, the patients with improved lung carcinoma and the healthy individuals, 8 proteins that are dipeptidyl peptidase Ⅳ, growth hormone, IL-4, myeloperoxidase, osteopontin, receptor of advanced glycation endproducts, TNF-α, and urokinase type plasminogen activator receptor with significant difference (P<0.05) were obtained. Clustering and analyzing data for all of the patients and the healthy individuals in the experiment found that the 8 proteins can very well distinguish the patients with advanced lung carcinoma from the patients with improved lung carcinoma and the healthy individuals. The Fisher model for lung carcinoma was confirmed. Conclusion: The solid phase antibody chip against multiple factors and optimal statistical methods could screen out the serum protein biomarkers related to occurrence, development and efficacy of lung carcinoma, which could establish a certain basis of clinical trail for researches on the mechanism of lung carcinogenesis as well as clinical diagnosis and treatment of the lung carcinoma. It could play an important guiding role in the individualized treatment of the lung carcinoma.
13 Connexin 43 enhances invasion capacity of bladder cancer cells through P38/MAPK signaling pathway
2017, 24(5):533-537.
DOI: 10.3872/j.issn.1007-385X.2017.05.013
Abstract:
Objective:To explore the effect of connexin 43(Cx43) on invasion ability of bladder cancer cells and the possible mechanisms. Methods: Fifty-two bladder cancer tissues and 32 precancerous tissues resected from June 2014 to September 2015 at the Department of Urology of the Affiliated Hospital of Chengde Medical University, as well as human bladder cancer 5637 cell line were collected for this study. Immunohistochemical method was used to detect the expression of Cx43 protein in bladder cancer tissues. Cx43 liposome plasmid (Transfection group), empty liposome plasmid (Transfection control group), siRNA (siRNA group) and siRNA control (siRNA control gorup) were transfected into bladder cancer 5637 cells. The efficiency of over-expression and knockdown was evaluated by Western blotting; the changes in invasion of bladder cancer cells were evaluated by Transwell assay. The changes in protein expressions of MMP-2, MMP-9, P38 and P-P38 were detected by Western blotting. Results: The expression of Cx43 protein in bladder cancer tissues was significantly higher than that in paracancerous tissues (\[5.21±0.33\] vs \[2.84±0.19\], P<0.01). Transfection of Cx43 liposome or siRNA successfully up-/down-regulated the expression of Cx43 in 5637 cells. Compared with control group, the migration ability of 5637 cells in Cx43 over-expression group was increased significantly (\[1.36±0.04\] vs \[0.70±0.15\]，P<0.01), while that of siRNA group was decreased significantly (\[0.20±0.08\] vs \[0.59±0.13\], P<0.05). The protein expressions of MMP-2, MMP-9, P-P38 and P38 in Cx43 liposome transfection group were significantly higher than those in control group (P<0.01 or P<0.05), while the expressions in siRNA group were significantly lower than those in the control group (all P<0.01). Conclusion: Cx43 could enhance invasion ability of bladder cancer cells, and the mechanism might be related with the activation of P38/MAPK signaling pathway.
Objective:To explore the effect of connexin 43(Cx43) on invasion ability of bladder cancer cells and the possible mechanisms. Methods: Fifty-two bladder cancer tissues and 32 precancerous tissues resected from June 2014 to September 2015 at the Department of Urology of the Affiliated Hospital of Chengde Medical University, as well as human bladder cancer 5637 cell line were collected for this study. Immunohistochemical method was used to detect the expression of Cx43 protein in bladder cancer tissues. Cx43 liposome plasmid (Transfection group), empty liposome plasmid (Transfection control group), siRNA (siRNA group) and siRNA control (siRNA control gorup) were transfected into bladder cancer 5637 cells. The efficiency of over-expression and knockdown was evaluated by Western blotting; the changes in invasion of bladder cancer cells were evaluated by Transwell assay. The changes in protein expressions of MMP-2, MMP-9, P38 and P-P38 were detected by Western blotting. Results: The expression of Cx43 protein in bladder cancer tissues was significantly higher than that in paracancerous tissues (\[5.21±0.33\] vs \[2.84±0.19\], P<0.01). Transfection of Cx43 liposome or siRNA successfully up-/down-regulated the expression of Cx43 in 5637 cells. Compared with control group, the migration ability of 5637 cells in Cx43 over-expression group was increased significantly (\[1.36±0.04\] vs \[0.70±0.15\]，P<0.01), while that of siRNA group was decreased significantly (\[0.20±0.08\] vs \[0.59±0.13\], P<0.05). The protein expressions of MMP-2, MMP-9, P-P38 and P38 in Cx43 liposome transfection group were significantly higher than those in control group (P<0.01 or P<0.05), while the expressions in siRNA group were significantly lower than those in the control group (all P<0.01). Conclusion: Cx43 could enhance invasion ability of bladder cancer cells, and the mechanism might be related with the activation of P38/MAPK signaling pathway.
2017, 24(5):538-543.
DOI: 10.3872/j.issn.1007-385X.2017.05.014
Abstract:
Objective:To investigate the relationship between miR-200c expression and the clinical pathologic characteristics and disease free survival (DFS) of gastric cancer patients. Methods: Sixty-four gastric cancer samples resected from May 2012 to January 2016 at General Surgery Department of the Fourth Hospital of Hebei Medical University were collected in this study, and the relative clinical data were retrospectively analyzed. Real-time fluorescence quantification PCR was adopted to detect the expression of miR-200c in the gastric cancer tissues and corresponding para-cancerous tissues. The correlation between miR-200c expression and clinicopathological features as well as DFS was retrospectively analyzed. Results: miR-200c was dramatically decreased in gastric cancer tissues when compared to the para-cancerous tissues (329 vs 5.91, P<0.01). miR-200c expression was negatively correlated with TNM stage, tumor infiltration depth (T), metastasis(M), venous tumor thrombus (; all P<0.01). The median DFS in high miR-200c expression group was significantly longer than that of low expression group (22.0 vs 13.5 months, P<0.01), indicating a positive correlation between miR-200c expression and DFS (r=0.54, P<0.01). Conclusion:miR-200c dramatically decreased in gastric cancer tissues. Its expression level was negatively correlated with TNM stage, tumor infiltration depth and venous tumor thrombus, but positively correlated with DFS. These data suggest it may play a protective role in progress and prognosis of gastric cancer.
Objective:To investigate the relationship between miR-200c expression and the clinical pathologic characteristics and disease free survival (DFS) of gastric cancer patients. Methods: Sixty-four gastric cancer samples resected from May 2012 to January 2016 at General Surgery Department of the Fourth Hospital of Hebei Medical University were collected in this study, and the relative clinical data were retrospectively analyzed. Real-time fluorescence quantification PCR was adopted to detect the expression of miR-200c in the gastric cancer tissues and corresponding para-cancerous tissues. The correlation between miR-200c expression and clinicopathological features as well as DFS was retrospectively analyzed. Results: miR-200c was dramatically decreased in gastric cancer tissues when compared to the para-cancerous tissues (329 vs 5.91, P<0.01). miR-200c expression was negatively correlated with TNM stage, tumor infiltration depth (T), metastasis(M), venous tumor thrombus (; all P<0.01). The median DFS in high miR-200c expression group was significantly longer than that of low expression group (22.0 vs 13.5 months, P<0.01), indicating a positive correlation between miR-200c expression and DFS (r=0.54, P<0.01). Conclusion:miR-200c dramatically decreased in gastric cancer tissues. Its expression level was negatively correlated with TNM stage, tumor infiltration depth and venous tumor thrombus, but positively correlated with DFS. These data suggest it may play a protective role in progress and prognosis of gastric cancer.
2017, 24(5):544-546.
DOI: 10.3872/j.issn.1007-385X.2017.05.015
Abstract:
目的：通过检测MHC-Ⅰ类分子链相关蛋白A/B（MHC class Ⅰ chain-related protein A/B，MICA/B）在HER2阳性乳腺癌组织中的表达水平，探讨其与患者临床病理特征的关系。方法:收集2009年1月至2010年6月在南方医科大学附属郑州人民医院乳腺外科手术切除的HER2阳性乳腺癌标本62例及其临床资料，免疫组化法检测乳腺癌组织中MICA/B的表达水平，分析其与患者临床病理特征的关系。结果：MICA/B表达率为90.32%，高表达为64.52%。MICA/B的表达与患者的临床分期、ER、PR表达有关（均P<0.05），与绝经、淋巴结转移、组织学分级无关（均P>0.05）。结论：MICA/B的表达可能与HER2阳性乳腺癌的发生发展有关，有望成为免疫治疗的新靶点。
目的：通过检测MHC-Ⅰ类分子链相关蛋白A/B（MHC class Ⅰ chain-related protein A/B，MICA/B）在HER2阳性乳腺癌组织中的表达水平，探讨其与患者临床病理特征的关系。方法:收集2009年1月至2010年6月在南方医科大学附属郑州人民医院乳腺外科手术切除的HER2阳性乳腺癌标本62例及其临床资料，免疫组化法检测乳腺癌组织中MICA/B的表达水平，分析其与患者临床病理特征的关系。结果：MICA/B表达率为90.32%，高表达为64.52%。MICA/B的表达与患者的临床分期、ER、PR表达有关（均P<0.05），与绝经、淋巴结转移、组织学分级无关（均P>0.05）。结论：MICA/B的表达可能与HER2阳性乳腺癌的发生发展有关，有望成为免疫治疗的新靶点。
2017, 24(5):547-552.
DOI: 10.3872/j.issn.1007-385X.2017.05.016
Abstract:
磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase, PI3K）/蛋白激酶 B(protein kinase B, Akt)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin, mTOR)信号通路是人体中的重要信号通路，通过逐级磷酸化下游蛋白发挥作用。非小细胞肺癌（non-small cell lung cancer，NSCLC）中存在该信号通路的异常活化。活化的信号通路可以改变NSCLC细胞的增殖、凋亡、侵袭和迁移等生物学特性从而影响其对治疗药物的反应及预后。针对该通路抑制剂的研究很多，部分抑制剂已进入临床研究阶段。PI3K抑制剂包括广谱PI3K抑制剂、亚型特异性的PI3K抑制剂和PI3K/mTOR双重抑制剂。PI3K抑制剂单药有效率较低，但与化疗药物或其他靶向药物联用取得了不错的临床效果，目前往往将PIK3CA突变以及抑癌基因PTEN的缺失作为预测疗效的指标，但准确性欠佳，进一步筛选疗效预测指标是目前面临的重要问题。
磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase, PI3K）/蛋白激酶 B(protein kinase B, Akt)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin, mTOR)信号通路是人体中的重要信号通路，通过逐级磷酸化下游蛋白发挥作用。非小细胞肺癌（non-small cell lung cancer，NSCLC）中存在该信号通路的异常活化。活化的信号通路可以改变NSCLC细胞的增殖、凋亡、侵袭和迁移等生物学特性从而影响其对治疗药物的反应及预后。针对该通路抑制剂的研究很多，部分抑制剂已进入临床研究阶段。PI3K抑制剂包括广谱PI3K抑制剂、亚型特异性的PI3K抑制剂和PI3K/mTOR双重抑制剂。PI3K抑制剂单药有效率较低，但与化疗药物或其他靶向药物联用取得了不错的临床效果，目前往往将PIK3CA突变以及抑癌基因PTEN的缺失作为预测疗效的指标，但准确性欠佳，进一步筛选疗效预测指标是目前面临的重要问题。
2017, 24(5):553-557.
DOI: 10.3872/j.issn.1007-385X.2017.05.017
Abstract:
卵巢癌是女性生殖系统恶性肿瘤病死率最高的疾病，多药耐药现象在卵巢癌治疗中普遍存在，严重影响治疗效果及卵巢癌患者的生存率。基因测序技术及生物信息学的迅猛发展使精确寻找癌症发生发展的关键靶点成为可能，分子进化理论研究为此提供了重要的理论及技术支持。卵巢癌患者及耐药相关突变基因包括 P53基因、BRCA1/BRCA2基因等等。分子进化理论可在确定导致癌症发生或耐药的关键突变位点方面提供新思路，该理论有助于从新的方向阐释癌细胞耐药的相关机制，从而更有针对性地提出治疗的有效措施。
卵巢癌是女性生殖系统恶性肿瘤病死率最高的疾病，多药耐药现象在卵巢癌治疗中普遍存在，严重影响治疗效果及卵巢癌患者的生存率。基因测序技术及生物信息学的迅猛发展使精确寻找癌症发生发展的关键靶点成为可能，分子进化理论研究为此提供了重要的理论及技术支持。卵巢癌患者及耐药相关突变基因包括 P53基因、BRCA1/BRCA2基因等等。分子进化理论可在确定导致癌症发生或耐药的关键突变位点方面提供新思路，该理论有助于从新的方向阐释癌细胞耐药的相关机制，从而更有针对性地提出治疗的有效措施。
2017, 24(5):558-566.
DOI: 10.3872/j.issn.1007-385X.2017.05.018
Abstract:
表观遗传修饰主要包括DNA甲基化、组蛋白修饰和染色质重塑等，DNA甲基化成为表观遗传学肿瘤研究的热点。DNA甲基化在基因的转录和转录后调控、miRNA基因表达调控和长链非编码RNA的转录后调控中发挥着关键作用，与肿瘤发生密切相关。DNA甲基化与miRNA在肿瘤中相互作用，两者之间存在反馈调节。PR结构域蛋白(PRDI-BF1 and RIZ homology domain containing protein,PRDM)基因甲基化在肺癌中发挥重要作用，P16、RASSF1A、FHIT等基因甲基化与肺癌密切相关；EGFR甲基化、miRNA启动子区的甲基化，长链非编码RNAHOTAIR 、TUG1等调控下游靶基因启动子区的甲基化均与肺癌密切相关。
表观遗传修饰主要包括DNA甲基化、组蛋白修饰和染色质重塑等，DNA甲基化成为表观遗传学肿瘤研究的热点。DNA甲基化在基因的转录和转录后调控、miRNA基因表达调控和长链非编码RNA的转录后调控中发挥着关键作用，与肿瘤发生密切相关。DNA甲基化与miRNA在肿瘤中相互作用，两者之间存在反馈调节。PR结构域蛋白(PRDI-BF1 and RIZ homology domain containing protein,PRDM)基因甲基化在肺癌中发挥重要作用，P16、RASSF1A、FHIT等基因甲基化与肺癌密切相关；EGFR甲基化、miRNA启动子区的甲基化，长链非编码RNAHOTAIR 、TUG1等调控下游靶基因启动子区的甲基化均与肺癌密切相关。
2017, 24(5):567-570.
DOI: 10.3872/j.issn.1007-385X.2017.05.019
Abstract:
TNF家族B细胞活化因子（B cell activating factor of the TNF family，BAFF）和增殖诱导配体（a proliferation inducing ligand，APRIL）具有较高的同源性。BAFF可分别与B细胞活化因子受体（BAFF-R）、B细胞成熟抗原（B cell maturation antigen，BCMA）和穿膜蛋白活化物（transmembrane activator and cyclophilin ligand interactor，TACI）3个受体结合，而APRIL则与受体BCMA、TACI结合发挥作用。近年来BAFF/APRIL及其受体的研究逐渐从自身免疫性疾病和实体肿瘤转移到了血液系统疾病中。本文对BAFF/APRIL及其受体在血液肿瘤性疾病，诸如慢性淋巴细胞白血病、急性淋巴细胞白血病、多发性骨髓瘤和淋巴瘤中的研究进展，包括BAFF/APRIL及其受体的功能、作用机制以及在治疗和预后中所起的作用等作一综述。
TNF家族B细胞活化因子（B cell activating factor of the TNF family，BAFF）和增殖诱导配体（a proliferation inducing ligand，APRIL）具有较高的同源性。BAFF可分别与B细胞活化因子受体（BAFF-R）、B细胞成熟抗原（B cell maturation antigen，BCMA）和穿膜蛋白活化物（transmembrane activator and cyclophilin ligand interactor，TACI）3个受体结合，而APRIL则与受体BCMA、TACI结合发挥作用。近年来BAFF/APRIL及其受体的研究逐渐从自身免疫性疾病和实体肿瘤转移到了血液系统疾病中。本文对BAFF/APRIL及其受体在血液肿瘤性疾病，诸如慢性淋巴细胞白血病、急性淋巴细胞白血病、多发性骨髓瘤和淋巴瘤中的研究进展，包括BAFF/APRIL及其受体的功能、作用机制以及在治疗和预后中所起的作用等作一综述。
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- 《中国肿瘤生物治疗杂志》
- 1994年创刊
- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
- 邮编：200433
- 电话：021-81871002-22
- 电子邮箱：cjcb@biother.cn
- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
- CN 31-1725/R
- 国内定价： ￥20元/册
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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.