二甲双胍联合顺铂抑制卵巢癌细胞体外生长、侵袭的实验研究

Metformin combined with cisplatin inhibits the ovarian cancer cell growth and invasion in vitro:An experimental study

目的:研究二甲双胍联合顺铂对卵巢癌细胞体外生长、侵袭相关基因表达的影响。方法:培养卵巢癌SKOV3细胞株,随机分为用无血清DMEM处理的对照组,用含有10μmol/L顺铂的无血清DMEM处理的DDP组,用含有10 mmol/L二甲双胍的无血清DMEM处理的MET组,用含有10μmol/L顺铂和10mmol/L二甲双胍的无血清DMEM处理的DDP+MET组。结果:处理后24小时,DDP组、MET组、DDP+MET组细胞中GRP78、TBX2、CyclinD1、Ki-67、MTA1、CTHRC1、Slug、MMP2的蛋白表达量均显著低于对照组,Fn14、NDRG2、SOCS1、Beclin1、ST7L的蛋白表达量均显著高于对照组;DDP+MET组细胞中GRP78、TBX2、CyclinD1、Ki-67、MTA1、CTHRC1、Slug、MMP2的蛋白表达量均显著低于DDP组、MET组,Fn14、NDRG2、SOCS1、Beclin1、ST7L的蛋白表达量均显著高于DDP组、MET组。结论:二甲双胍联合顺铂对卵巢癌细胞中促增殖及侵袭基因的表达具有抑制作用、对促凋亡基因的表达具有促进作用,进而能够抑制癌细胞的生长、侵袭。

Objective:To study the effect of metformin combined with cisplatin on the expression of genes related to ovarian cancer cell growth and invasion in vitro.Methods:SKOV3 ovarian cancer cell lines were cultured and randomly divided into the control group treated with serum-free DMEM,the DDP group treated with serum-free DMEM containing 10μmol/L cisplatin,the MET group treated with serum-free DMEM containing 10 mmol/L metformin and the DDP+MET group treated with serum-free DMEM containing 10μmol/L cisplatin and 10 mmol/L metformin.Results:24 hours after treatment,GRP78,TBX2,CyclinD1,Ki-67,MTA1,CTHRC1,Slug and MMP2 protein expression in DDP group,MET group and DDP+MET group were significantly lower than those in control group whereas Fn14,NDRG2,SOCS1,Beclin1 and ST7 Lprotein expression were significantly higher than those of control group;GRP78,TBX2,CyclinD1,Ki-67,MTA1,CTHRC1,Slug and MMP2 protein expression in DDP+ MET group were significantly lower than those in DDP group and MET group whereas Fn14,NDRG2,SOCS1,Beclin1 and ST7 Lprotein expression were significantly higher than those in DDP group and MET group.Conclusion:metformin combined with cisplatin can inhibit the expression of pro-proliferation and invasion genes and promote the expression of pro-apoptosis genes in ovarian cancer cells so as to inhibit cancer cell growth and invasion.