二甲双胍对SKM-1细胞增殖抑制作用及相关作用机制

Inhibitory Effects of Metformin on Proliferation of SKM-1 Cells and The Related Underlying Mechanisms

目的:探讨二甲双胍对AML-MDS细胞株SKM-1细胞增殖的影响以及相关的机制。方法:采用CCK-8检测细胞增殖;采用流式细胞术检测细胞凋亡和细胞周期;采用蛋白印迹法检测通路蛋白AMPK和周期相关蛋白的表达水平。结果:二甲双胍可抑制SKM-1细胞增殖,该作用依赖于二甲双胍诱导细胞周期G0/G1期停滞而非促进细胞凋亡。G1期相关周期蛋白(CyclinD1、CDK4)表达水平明显下调,而周期抑制蛋白P53、P21^CIP1、P27^KIP1的蛋白水平上调。此外,与二甲双胍抗肿瘤效应相关的AMPK蛋白磷酸化水平上调。结论:二甲双胍抑制SKM-1细胞增殖活性,这可能与其激活AMPK通路诱导细胞周期停滞有关,但仍需进一步深入研究其相关机制。

Objective:To investigate the effects of metformin on the proliferation of AML-MDS cells(SKM-1 cells)and its related mechanisms.Methods:CCK-8 was used to test the cell proliferation;Flow cytometry was used to detect the cell apoptosis and cell cycle;Western blot was used to test the expression level of AMPK and cell cycle regulatory proteins.Results:Metformin could inhibit the proliferation of SKM-1 cells,which may be attributed to metformininduced cell cycle arrest in G0/G1 but not to metformin induced cell apoptosis.The expression levels of G1-related protein CyclinD1 and CDK4 were down-regulated,while the expression levels of P53,P21^CIP1 and P27^KIP1 were up-regulated.Moreover,the phosphorylation level of AMPK was up-regulated.Conclusion:Metformin inhibits the proliferation of SKM-1 cells,which may relate with AMPK-induced cell cycle arrest.However,future studies are necessary to further explore the related mechanisms.