摘要
目的:探讨二甲双胍(Met)对肾癌细胞增殖、迁移与凋亡的影响及其机制。方法:将培养的786-O细胞和ACHN细胞随机分为对照组和处理组,对照组细胞用正常培养基培养,处理组分别用含1 mmol/L、5 mmol/L、10 mmol/L的Met培养基培养。采用CCK-8检测不同浓度Met作用24 h、48 h、72 h后各组细胞的增殖抑制率,流式细胞仪检测各组细胞的周期分布与凋亡情况,Transwell小室实验和细胞划痕实验检测各组细胞迁移,Western blot检测磷脂酰肌醇-3-激酶/蛋白激酶B(PI3K/AKT)信号通路相关蛋白的表达水平。结果:不同浓度的Met作用于786-O细胞和ACHN细胞后,细胞增殖抑制率较对照组显著升高(P<0.01),且呈现浓度与时间依赖性(P<0.01);与对照组比较,经不同浓度Met作用后,可使786-O细胞和ACHN细胞均发生S期阻滞(P<0.01),抑制细胞的迁移(P<0.01),并促进细胞的凋亡(P<0.01),且呈浓度依赖性;786-O细胞中p-PI3K与p-AKT蛋白表达量较对照组显著下降(P<0.05)。结论:Met可抑制肾癌细胞增殖,使细胞周期停滞在S期,并抑制细胞的迁移,并促进细胞凋亡,其机制可能与抑制PI3K/AKT信号通路有关。
Objective:To investigate the effect and its mechanism of metformin(Met)on proliferation,migration and apoptosis of renal cancer cells.Methods:The cultured786-O cells and ACHN cells were randomly divided into control group and treatment group.The cells in control group were cultured in normal medium,and the cells in treatment group were cultured in Met medium containing 1mmol/L,5mmol/L and 10 mmol/L,respectively.CCK-8 method was used to detect the proliferation inhibition rate of cells treated with different concentrations of Met for 24 h,48 h and 72 h.Flow cytometry was used to detect the cell cycle distribution and apoptosis.Transwell chamber test and cell scratch test were used to detect cell migration in each group.Western blot was used to detect the expression of phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)signal pathway related proteins.Results:The cell proliferation inhibition rate of 786-O cells and ACHN cells treated with different concentrations of Met was significantly higher than that of the control group(P<0.01),and showed concentration and time dependence(P<0.01).Compared with the control group,different concentrations of Met blocked the S phase(P<0.01),inhibited the cell migration(P<0.01)and promoted the apoptosis of 786-cells and ACHN cells(P<0.01),and showed concentration dependence.The protein expression of p-PI3K and p-AKT in 786-cells was significantly lower than that in the control group(P<0.05).Conclusion:Met can inhibit the proliferation of renal cancer cells,arrest the cell cycle in S phase,inhibit cell migration and promote apoptosis.The mechanism may be related to the inhibition of PI3K/AKT signal pathway.
作者
张鑫
杜伟
Zhang Xin;Du Wei(Urology,Fuling Central Hospital,Chongqing 408000,China)
出处
《广西医科大学学报》
CAS
2020年第8期1505-1511,共7页
Journal of Guangxi Medical University
