二甲双胍对肝癌细胞增殖及凋亡相关基因表达的影响  

Effects of metformin on apoptosis and the expression of apoptosis-related genes of Hep-G2 cells

作　　者：卢清军[1] 熊宇[1] 严威[1] 林芬[1] 王效民[1] 吴国洋[1] 

机构地区：[1]厦门大学附属中山医院肝胆外科,361005

出　　处：《中华实验外科杂志》2011年第7期1107-1110,共4页Chinese Journal of Experimental Surgery

基　　金：重大传染病防治重大科技专项基金资助项目（2008Ex100-02019）

摘　　要：目的观察二甲双胍对人肝癌Hep—G2细胞增殖、凋亡及裸鼠皮下瘤生长的影响。方法噻唑蓝（MTT）比色法分别检测二甲双胍作用于细胞后其细胞活力及生长抑制率；流式细胞术检测二甲双胍作用后细胞周期时相、凋亡率；免疫印迹法（Western blot）检测凋亡相关蛋白的表达；将Hep—G2细胞接种丁裸鼠，观察不同浓度二甲双胍对裸鼠皮F瘤生长的影响。结果20mmol／L二甲双胍作用细胞48h时，细胞生长周期阻滞于G0／G1期，细胞凋亡率为（20．57±3．16）％；Western blot检测显示bcl-2、bcl-xl蛋白表达随着药物浓度的增加而减少，Bid蛋白表达随着药物浓度增加而增加。高剂量二甲双胍组及联合用药组裸鼠皮下瘤体积显著小于对照组，20d时两组抑瘤率分别为40．8％、72．8％。结论二甲双胍通过线粒体介导的凋亡通路途径来诱导人肝癌细胞发生凋亡，并抑制肝癌细胞裸鼠瘤生长。Objective To investigate the effect of metformin on proliferation, apoptosis of Hep-G2 cells and tumor growth in nude mice. Methods Hep-G2 cells were treated with metformin at different concentrations, and cell viability was measured by using methyl thiazol tetrazolium （MTF） method. Cell cycle and apoptosis rate were assayed by flow cytometry. The expression of apoptosis-related protein were detected by Western blotting. Nude mice were transplanted with Hep-G2 cells, and tumor growth inhibition rate was detected. Results After Hep-G2 cells were treated with 20 mmol/L metformin for 48 h, the growth cycle was arrested in G0/G1 phase, the apoptosis rate was （20. 57 ± 3. 16）% , the expression of bcl-2 and bcl-xl proteins was down-regulated after metformin treatment, while the Bid protein was significantly increased, tumor size in the high-dose metformin group, cisplatin combined with metformin group were significantly reduced as compared with control group, and the inhibition rates in the high-dose metformin group, cisplatin combined with metformin group was 40. 8% and 72. 8% respectively. Conclusion Metformin inhibits proliferation of Hep-G2 cells, and induces apoptosis in, vitro and significantly inhibits the growth of hepatocellular carcinoma in nude mice.

关 键 词：二甲双胍 癌 肝细胞 脱噬作用 

分 类 号：R735.7[医药卫生—肿瘤]