二甲双胍对结肠癌细胞增殖的影响

The influence of metformin on colon cancer cell growth

目的研究发现,二甲双胍在多种肿瘤中显示出抗肿瘤作用。在结直肠癌中,二甲双胍对肿瘤的抑制作用机制尚不明确,本研究旨在探究二甲双胍对结肠癌细胞增殖的影响。方法 MTT实验检测不同浓度的二甲双胍对HT29结肠癌细胞增殖率变化的影响。利用蛋白免疫印迹方法检测二甲双胍作用下的HT29结肠癌细胞增殖相关蛋白表达的变化。结果二甲双胍能够抑制结肠癌HT29细胞的增殖且呈浓度依赖性。利用二甲双胍处理HT29细胞不同时间点后发现,二甲双胍能够抑制蛋白激酶B(Akt)与细胞外调节蛋白激酶(ERK)的磷酸化水平。进一步研究证实,二甲双胍能够抑制结肠癌细胞Akt、Erk上游IGF1R磷酸化水平。结论二甲双胍能够通过阻断胰岛素样生长因子受体(IGF1R)进而抑制下游Akt、Erk信号抑制结肠癌HT29细胞增殖。

Objective The antitumor effect of metformin have been explored in various type of cancers. In colorectal cancer, the mechanism of inhibition effect of metformin is unclear. Thus, the purpose of the present study is to investigate the effect of metformin on proliferation of colon cancer cells.MethodsThe variation of proliferation rate of HT29 colon cancer cell line was detected by MTT assay. Western Blotting assay was performed to test the variation of protein expression level in metformin treated HT29 cells.Results Metformin could inhibit proliferation of HT29 cells which present concentration dependence. After metformin treated HT29 cells for different duration, protein kinase B （Akt） and extracellular regulated protein kinases （Erk） phosphorylation were down-regulated. Further investigation showed that metformin could inhibit insulin-like growth factor 1 receptor （IGF1R） phosphorylation level which is the upstream of Akt and Erk signaling pathway in HT29 cells.ConclusionMetformin inhibit proliferation of HT29 colon cancer cell by blocking IGF1R and downstream Akt and Erk signaling pathway.