二甲双胍通过抑制MAPK信号通路增强卵巢癌细胞对顺铂的敏感性

Metformin Enhances Cisplatin Sensitivity through Activating MAPK Signaling Pathway in Ovarian Cancer

目的:探讨二甲双胍是否可以提高卵巢癌细胞对顺铂的敏感性及相关的作用机制。方法:BRDU ELISA方法检测顺铂联合或者不联合二甲双胍对SKOV3细胞增殖的影响;二甲双胍联合或者不联合MAPK信号通路阻断剂后BRDU ELISA方法检测细胞增殖的变化。Western blotting检测二甲双胍作用下卵巢癌细胞系SKOV3的磷酸化AMPK/总AMPK水平和磷酸化p38 MAPK/总MAPK水平的变化。结果:(1)二甲双胍不仅能抑制卵巢癌细胞系SKOV3细胞的增殖,而且能提高对顺铂的敏感性,并且这种作用是依赖于AMPK激活的;(2)p38 MAPK阻断剂SB203580能够抑制SKOV3的增殖,二甲双胍能够增强这种抑制作用。结论:二甲双胍可增强顺铂对卵巢癌细胞的抑制作用,并且二甲双胍可能通过激活AMPK信号通路进而抑制MAPK信号通路增加顺铂对卵巢癌细胞的抑制增殖作用。

Objective：To investigate metformin whether improve the sensitivity of cisplatin in ovarian cancer and explore the underlying mechanisms. Method：Ovarian cancer cell line SKOV3 was used. The expression of phosphorylated p38MAPK and AMPK were confirmed in ovarian cancer cells by Western blotting. BRDU ELISA KIT was used to analyze the effects of metformin ,SB203580（p38MAPK inhibitor）and cisplatin alone or together in ovarian cancer cells. Result：（1） Metformin could not only inhibit the proliferation of ovarian cancer cell line SKOV3 cells,but also improve the sensitivity to cisplatin,which is dependent on the activation of AMPK.（2）SB203580,the p38 MAPK inhibitor,could also inhibit the proliferation of SKOV3,which could be enhanced by metformin. Conclusion：Metformin may enhance cisplatin sensitivity through activating MAPK signaling pathway in ovarian cancer cells.