二甲双胍对卵巢癌细胞的抗肿瘤作用  

Antitumor Effect of Metformin on Ovarian Cancer Cells

作　　者：余慧[1] 李臻 王佳[1] YU Hui;LI Zhen;WANG Jia(Department of Obstetrics and Gynecology,The First Affiliated Hospital of Xi’an Jiao Tong University,Xi’an 710061,China)

机构地区：[1]西安交通大学第一附属医院妇产科,西安710061

出　　处：《肿瘤防治研究》2024年第1期27-33,共7页Cancer Research on Prevention and Treatment

基　　金：陕西省重点研发计划项目(2020SF-030)。

摘　　要：目的探讨二甲双胍对卵巢癌细胞增殖、周期、凋亡和迁移的影响及其作用机制。方法选取卵巢癌A2780、CAOV3、SKOV3细胞为研究对象,MTT和克隆形成实验检测二甲双胍对细胞增殖的影响,划痕实验和Transwell实验检测二甲双胍对细胞迁移能力的影响,流式细胞术检测二甲双胍对细胞周期和凋亡的影响,Western blot法检测二甲双胍对细胞AMPK磷酸化、mTOR磷酸化、CXCR4和Wnt/β-catenin蛋白表达的影响。结果随着二甲双胍浓度增加和作用时间延长,卵巢癌细胞存活率明显下降。A2780、CAOV3及SKOV3细胞48 h的IC_(50)分别为16.36、36.65和43.44 mmol/L。与对照组相比,二甲双胍处理后,细胞克隆形成能力和迁移能力被明显抑制,细胞周期阻滞于G_(0)/G_(1)期,细胞凋亡率增加。随着二甲双胍浓度增加,磷酸化AMPK蛋白表达逐渐增加,磷酸化mTOR、CXCR4、Dvl3、β-catenin、CyclinD1、CDK1蛋白表达逐渐降低。结论二甲双胍对卵巢癌细胞具有抗肿瘤作用,其机制可能与激活AMPK抑制CXCR4介导的Wnt/β-catenin信号通路有关。Objective To explore the antitumor effects of metformin on ovarian cancer cells in vitro,particularly on tumor cell proliferation,cell cycle,apoptosis,migration,and possible mechanism.Methods Ovarian cancer cell lines(A2780,CAOV3,and SKOV3)were treated with different concentrations of metformin.Their proliferation was explored using the MTT and clone formation assays,cell migration was examined using the scratch and Transwell assays,and cell cycle and apoptosis were examined using flow cytometry.In addition,metformin’s effects on the phosphorylation of AMPK and mTOR and the expression of CXCR4 and Wnt/β-catenin protein was measured by Western blot.Results The survival rates of ovarian cancer cells decreased significantly with increasing metformin concentration and metformin treatment time.The IC_(50) values of metformin at 48 h for A2780,CAOV3,and SKOV3 cells were 16.36,36.65,and 43.44 mmol/L,respectively.Compared with the control group,the clone formation ability and cell migration ability of ovarian cancer cells were significantly inhibited by metformin treatment and cell cycle arrested at the G_(0)/G_(1) phase,and the apoptosis rate increased.As metformin concentration increased,the expression of phosphorylated AMPK protein gradually increased,and the expression levels of phosphorylated mTOR,CXCR4,Dvl3,β-catenin,cyclin D1,and CDK1 decreased.Conclusion Metformin exerts an antitumor effect on ovarian cancer cells,which is related to the activation of AMPK to inhibit CXCR4-mediated Wnt/β-catenin signaling pathway.

关 键 词：二甲双胍 卵巢癌 增殖 迁移 趋化因子受体4 

分 类 号：R737.31[医药卫生—肿瘤]