| 滕小路,刘 淼,张腾跃.维拉帕米通过调节Bcl-２表达对胃癌细胞株耐阿霉素的影响[J].肿瘤学杂志,2018,24(4):328-335. |
| 维拉帕米通过调节Bcl-２表达对胃癌细胞株耐阿霉素的影响 |
| Bcl-2 Targeted by Verapamil in the Prevention of Drug Resistance to Adriamycin in Gastric Cancer Cells |
| 投稿时间：2017-07-01 |
| DOI：10.11735/j.issn.1671-170X.2018.04.B008 |
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| 中文关键词: 胃肿瘤 维拉帕米 多柔比星 耐药性 Bcl-２ |
| 英文关键词:gastric cancer verapamil doxorubicin drug-resistance Bcl-2 |
| 基金项目:国家自然科学基金（81350005）；安徽省科技厅2012年度重点科研计划项目（12070403058）；安徽省自然科学基金（1408085MH211）；安徽省“十二五”临床重点专科建设项目，安徽省自然科学基金（1708085MH228） |
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| 中文摘要: |
| 摘 要：［目的］ 探讨Bcl-２在维拉帕米逆转胃癌阿霉素化疗耐药中的作用及初步机制研究。［方法］ MTT法检测维拉帕米逆转胃癌细胞系(SGC-7901、BGC-823、AGS、HGC-27) 对3种化疗药物（氟尿嘧啶、阿霉素、顺铂）的耐药能力；流式细胞仪Annexin V-FITC/PI法检测维拉帕米对阿霉素作用下的胃癌细胞系（SGC-7901、HGC-27）凋亡水平的影响。Western blotting检测Bcl-２蛋白表达水平。［结果］ SGC-7901细胞系在单药阿霉素组和阿霉素联合维拉帕米组中的半数抑制浓度（IC50）分别为1.51±0.12μg/ml、0.22±0.01μg/ml，两组差异有统计学意义（P＜0.05）；HGC-27细胞中分别为1.24±0.19μg/ml、1.06±0.08μg/ml，两组差异无统计学意义（P＞0.05）。凋亡实验表明在SGC-7901细胞系中，单药阿霉素组中的细胞凋亡率为36.76%，阿霉素联合维拉帕米组为61.10%，两组比较差异有统计学意义(P＜0.05)。HGC-27细胞系中，阿霉素组细胞凋亡率19.79%，阿霉素联合维拉帕米组为21.92%，两组比较差异无统计学意义(P>0.05)。SGC-7901细胞中维拉帕米促进ADM组胃癌细胞凋亡指数明显高于HGC-27(P＜0.05)。qRT-PCR实验显示Bcl-２可能介导维拉帕米促进胃癌细胞凋亡；Western blotting结果显示在SGC-7901细胞中，阿霉素联合维拉帕米组Bcl-２的表达明显低于单药阿霉素组，与对照组比较差异有统计学意义(P＜0.05)；而HGC-27中2组间差异无统计学意义。［结论］ 维拉帕米通过下调Bcl-２表达增强维拉帕米逆转胃癌细胞化疗耐受的能力，并促进胃癌细胞凋亡。 |
| 英文摘要: |
| Abstract：［Objective］To investigate the chemotherapy resistance reversal in gastric cancer cells with verapamil，screen the target gene Bcl-2 associated with the above reversal process and study its mechanism. ［Methods］ The ability of verapamil in reversing the chemotherapy resistance of fluorouracil，doxorubicin and cisplatin in gastric cancer cell lines SGC-7901，BGC-823，AGS and HGC-27 was detected with the CCK-8 method. The effect of verapamil on the apoptosis of doxorubicin-based gastric cancer cell lines(SGC-7901，HGC-27) was also tested with the Annexin V-FITC/PI method. The protein expression levels of Bcl-2 were detected with Western blotting. ［Results］ The IC50 values of SGC-7901 cell lines in ADM(adriamycin) group and ADM-VRP(adriamycin-verapamil) combination group were 1.51±0.12μg/ml and 0.22±0.01μg/ml，respectively，there was an obvious difference between the two groups(P<0.05). The IC50 values of HGC-27 cells were 1.24±0.19μg/ml and 1.06±0.08μg/ml，there was no obvious difference between the two groups(P＞0.05). The apoptosis experiment showed that apoptosis rates of the SGC-7901 cell line in ADM group and ADM-VRP combination group were 36.76% and 61.10%，respectively. The data were significantly different from that of the blank group(P<0.05). Apoptosis rates of the HGC-27 cell line in ADM group and ADM-VRP combination group were 19.79% and 21.92%，respectively. The apoptosis index of the SGC-7901 cells promoted by verapamil in ADM group was significantly higher than that of HGC-27 cells，and there was a significant difference between them(P<0.05). A qRT-PCR experiment results showed that Bcl-2 might mediate verapamil in promoting the apoptosis of gastric cancer cells. Western blotting results showed that the Bcl-2 expression in SGC-7901 cells treated with the combination of adriamycin and verapamil was significantly lower than that treated with adriamycin alone(P＜0.05). The data had significant differences with the control group while the differences among the four HGC-27 cell groups were not significant. ［Conclusion］ Verapamil by down-regulated the Bcl-2 gene expression enhanced ability of the resistance of verapamil reverse gastric cancer cells to chemotherapy，and promote the gastric cancer cell apoptosis. |
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