二甲双胍对DEHP和DBP诱导的MCF-7细胞增殖和迁移的抑制作用  

Inhibition of metformin on phthalate-induced proliferation and migration of MCF-7 breast cancer cells

作　　者：程斌 王新宇 孙钰 张家泰 董淑英[1] CHENG Bin;WANG Xinyu;SUN Yu;ZHANG Jiatai;DONG Shuying(Department of Occupational and Environmental Health Sciences,School of Public Health,Harbin Medical University,Harbin 150081,Heilongjiang;Shanghai University of Medicine&Health Sciences,Shanghai 201318,China)

机构地区：[1]哈尔滨医科大学公共卫生学院环境卫生教研室,黑龙江哈尔滨150081 [2]上海健康医学院,上海201318

出　　处：《癌变．畸变．突变》2021年第3期197-202,共6页Carcinogenesis,Teratogenesis & Mutagenesis

摘　　要：目的:研究二甲双胍对邻苯二甲酸二(2-乙基己)酯(DEHP)和邻苯二甲酸二正丁酯(DBP)诱导的乳腺癌MCF-7细胞增殖和迁移的抑制作用。方法:设不同浓度的DEHP(20、40、100、200、400μg/mL)、DBP(0.14、0.28、0.7、1.4、2.8、14、28μg/L)、二甲双胍(2.5、5、10、20 mg/mL)单独染毒组和溶剂对照组(0.1%二甲基亚砜),并将20 mg/mL二甲双胍分别加入DEHP(100μg/mL)和DBP(0.7μg/L)中,采用四甲基噻唑蓝(MTT)实验检测MCF-7细胞的增殖情况,观察细胞形态学变化,用划痕修复实验和Transwell实验检测MCF-7细胞迁移情况。结果:与溶剂对照组相比,DEHP(20~400μg/mL)、DBP(0.14~28μg/L)单独染毒组使MCF-7细胞增殖率升高,细胞迁移能力增强,差异均有统计学意义(P<0.05);二甲双胍(2.5~20 mg/mL)单独染毒组使MCF-7细胞增殖率明显降低,细胞迁移能力减弱,差异有统计学意义(P<0.05)。与DEHP和DBP单独染毒组比较,二甲双胍联合DEHP和DBP组,MCF-7细胞的增殖率下降,细胞迁移能力减弱,差异有统计学意义(P<0.05)。结论:DEHP和DBP可以诱导人乳腺癌MCF-7细胞的增殖和迁移,二甲双胍可以抑制其增殖和迁移作用。OBJECTIVE:This study aims to explore induction of proliferation and migration in MCF-7 breast cancer cells by phthalates(DEHP,DBP)as well as their inhibition by metformin.METHODS:MCF-7 cells were treated with DEHP(20,40,100,200 and 400μg/mL),DBP(0.14,0.28,0.7,1.4,2.8,14,28μg/L)or metformin(2.5,5,10,20 mg/mL).Untreated cells were used as controls.20 mg/mL metformin was added to DEHP(100μg/mL)and DBP(0.7μg/L)respectively.The effects of DEHP and DBP on induction of proliferation of MCF-7 cells,and inhibitory effects of metformin were detected by MTT assay.Effects of DEHP and DBP on migration of MCF-7 cells and the inhibitory effects of metformin were detected by the wound healing and Transwell assay.RESULTS:Compared with the control group,MTT and cell migration assays revealed that DEHP(20-400μg/mL)and DBP(0.14-28μg/L)treatments significantly increased cell proliferation and migration in MCF-7.On the other hand,metformin(2.5-20 mg/mL)treatment diminished cell proliferation and migration(P<0.05).Compared with the DEHP and DBP groups,the combined exposures to phthalate(100μg/mL DEHP,0.7μg/L DBP)and metformin(20 mg/mL)diminished cell proliferation and migration of MCF-7 cells.CONCLUSION:The present study demonstrates that metformin inhibited proliferation and migration of MCF-7 breast cancer cells which were induced by DEHP and DBP.

关 键 词：邻苯二甲酸酯 邻苯二甲酸二(2-乙基己)酯 邻苯二甲酸二正丁酯 乳腺癌细胞 二甲双胍 

分 类 号：R737.9[医药卫生—肿瘤]