目的:探讨二甲双胍联合表皮生长因子受体(EGFR)信号通路阻断剂对子宫内膜癌细胞增殖的影响及相关的作用机制。方法:选取子宫内膜癌Ishikawa及HEC-1A细胞,CCK-8方法检测二甲双胍联合或者不联合EGFR信号通路抑制剂AG1478对子宫内膜癌细胞增殖的影响。RT-PCR检测二甲双胍对EGFR mRNA的影响。Western blotting检测二甲双胍作用下子宫内膜癌细胞磷酸化EGFR/总EGFR和磷酸化ERK/总ERK水平的变化。结果:1AG1478能够抑制子宫内膜癌细胞的增殖,二甲双胍能够增强其抑制作用;2二甲双胍抑制EGFR mRNA的表达;3二甲双胍能够抑制EGFR及ERK磷酸化蛋白的表达。结论:二甲双胍能够增强EGFR信号通路阻断剂AG1478对子宫内膜癌的抑制作用;并且二甲双胍可能通过抑制EGFR磷酸化蛋白的表达从而抑制ERK蛋白的磷酸化进而抑制子宫内膜癌细胞的增殖。
Objective: To explore the effect of metformin combined with epidermal growth factor receptor (EGFR) signaling path- way inhibitor on proliferation of endometrial cancer cells and the related mechanism. Methods : Endometrial cancer Ishikawa and HEC - 1A cells were selected. The effects of metformin combined with AG1478 and simple metformin on proliferation of endometrial cancer cells were detected by CCK - 8 method. The effect of metformin on EGFR mRNA was detected by RT - PCR. After treated with metformin, the changes of pEGFR/t - EGFR and pERK/t - ERK ratios in endometrial cells were detected by Western blotting. Results: AG1478 inhibited proliferation of endometrial cancer cells, metformin enhanced the effect. Metformin inhibited the expression of EGFR mRNA. Metformin inhibited the expressions of pEGFR and pERK. Conclusion : Metformin can enhance the inhibitory effect of AG1478 on proliferation of endometrial cancer ceils. Metformin can significantly inhibit proliferation of endometrial cancer cells by inhibiting pEGFR expression and pERK expression.