二甲双胍联合奥沙利铂对胃癌SGC-7901细胞增殖抑制及诱导凋亡作用的研究  

Effect of metformin combined with exaliplatin on cell proliferation and apoptosis of gastriccancer cell line SGC-7901

作　　者：蔡珍华 郭岚岚 黄志高 张晨禹 朱军[2] 王亮[2] 刘开渊 

机构地区：[1]解放军第九五医院消化内科,福建莆田351100 [2]第四军医大学西京医院消化内科

出　　处：《中国医师进修杂志》2017年第12期1057-1061,共5页Chinese Journal of Postgraduates of Medicine

摘　　要：目的 评价二甲双胍联合奥沙利铂抑制胃癌SGC-7901细胞体外增殖和凋亡的影响,比较二甲双胍联合奥沙利铂与分别单独用药对胃癌SGC-7901细胞的杀伤效应.方法 体外培养人胃癌SGC-7901细胞,采用MTT法检测不同浓度二甲双胍（5.0、10.0、15.0 mmol/L）、奥沙利铂（2.5、5.0、10.0 μmol/L）及15.0 mmol/L二甲双胍联合10.0 μmol/L奥沙利铂处理胃癌SCG-7901细胞24、48、72 h的增殖抑制率,采用流式细胞仪检测细胞凋亡率,采用Western blot法检测药物处理对caspase-3、Bax蛋白的活化情况.结果 二甲双胍及奥沙利铂单药均能抑制胃癌SGC-7901细胞增殖,且呈现剂量时间依赖效应,联合用药组细胞增殖的抑制率明显高于单药组,差异有统计学意义（P〈0.05）.药物作用于细胞24 h后,经流式细胞仪检测15.0 mmol/L二甲双胍、10.0 μmol/L奥沙利铂及联合用药组细胞凋亡率分别为（16.0±2.1）%、（19.0±2.7）%、（29.0±3.5）%,与空白对照组的（10.0 ± 1.1）%比较差异有统计学意义（P〈0.05）.Western blot法检测结果显示,二甲双胍组、奥沙利铂组单药用于胃癌细胞24 h后,与空白对照组相比,均能提高caspase-3及Bax活性.而联合用药组caspase-3及Bax活性显著高于二甲双胍组、奥沙利铂组,差异有统计学意义（P〈0.05）.结论 二甲双胍能够显著增强奥沙利铂的胃癌SGC-7901细胞增殖抑制,诱导凋亡,其机制可能与上调caspase-3、Bax蛋白有关.Objective To investigate the effects of metformin and exaliplatin on proliferation and apoptosis of gastric cancer cell line SGC-7901. The antitumor effects of metformin combined with exaliplatin on gastric cancer cell line SGC-7901 were compared. Methods SGC-7901 cells were cultured in vitro. The proliferation inhibition rate of cancer cell after treatment with various concentrations of metformin（5.0,10.0,15.0 mmol/L）、exaliplatin（2.5,5.0,10.0 μmol/L）or 15.0 mmol/L metformin combined with 10.0 μmol/L exaliplatin was analyzed via MTT colorimetric assay at 24,48,72 h.After 24 h, the SGC-7901 cell apoptosis was detected by flow cytometry, and the relative activity of caspase-3 and bax was detected by western blot. Results The co-administration of metformin and exaliplatin or single agent treatment could increase the proliferation inhibition rates of SGC-7901 cell in a time-and dose-dependent manner, while there was a significant higher proliferation inhibition rate in co-administration versus single-agent treatment （P 〈 0.05）. The apoptosis rate induced by 15.0 mmol/L metformin and 10.0 μmol/L exaliplatin and combined treatment was （16.0 ± 2.1）%, （19.0 ± 2.7）%, （29.0 ± 3.5）%, higher than that in blank control group （10.0 ± 1.1）%, and there was significant difference （P 〈0.05）. Both of metformin and exaliplatin could increase caspase-3 and Bax activity.Caspase-3 and Bax activity in the combination of metformin and exaliplatin was significantly higher than that of metformin group and exaliplatin group （P 〈 0.05）. Conclusions Metformin combined with exaliplatin has synergistic effect in inhibiting the growth and inducing apoptosis of gastric cancer cell line SGC-7901.Enhancing caspase-3 and Bax expression may be the related mechanism

关 键 词：胃肿瘤 细胞凋亡 二甲双胍 奥沙利铂 对比研究 

分 类 号：R735.2[医药卫生—肿瘤]