重金属污染物镉通过EMT机制加强结肠癌细胞株HCT-116的恶性生物学行为  

Heavy metal pollutant cadmium enhances malignant biological behavior of human colorectal carcinoma HCT-116 cells via inducing epithelialmesenchymal transition

作　　者：钱燕[1,2] 陈丹蕾[1] 任海风 王仕清 于丹丹[1] 汪思应[1] 

机构地区：[1]安徽医科大学基础医学院病理生理学教研室,安徽省合肥市230032 [2]安庆医药高等专科学校生理病理教研室,安徽省安庆市246052

出　　处：《世界华人消化杂志》2016年第30期4185-4192,共8页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;Nos.81272258;81572749~~

摘　　要：目的探讨重金属污染物镉(cadmium,Cd)对人结肠癌细胞株HCT-116的恶性生物学行为的影响及其相关机制.方法选用低浓度Cd诱导的人类结肠癌稳定细胞株HCT-116和未诱导的细胞株HCT-116为研究对象.通过MTT实验、平板克隆形成实验、黏附实验、Tran swell细胞迁移和侵袭实验等,观察HCT-116细胞的恶性生物学行为的变化;蛋白免疫印迹法检测E-cadherin、Vimentin、E-盒结合锌指蛋白1、MMP-3、MMP-9等上皮-间质转化(epithelial-mesenchymal transition,EMT)相关蛋白的表达水平.结果与对照组相比,Cd诱导组细胞的恶性生物学行为增强(P<0.05),且转化后的细胞间呈间充质样链接;相较于对照组,Cd诱导24 h后,间质样标志物Vimentin蛋白的相对表达量明显增加(2.20±0.11 vs 1.03±0.08,P<0.01)、MMP-3(5.76±0.20 vs 1.00±0.09,P<0.01)、MMP-9(3-46±0.05 vs 0.99±0.04,P<0.01)的蛋白相对表达量也上升,而上皮样标志物E-cadherin蛋白的相对表达显著下降(0.30±0.03 vs 1.0l±0.05,P<0.01),且他们均呈现时司依赖性结论形态学和分子生物学都提示HCT-116细胞在慢性低剂量Cd暴露后会引起EMT机制.AIM To investigate the influence of cadmium on the malignant biological behavior of HCT-116 cells and the mechanism involved.METHODS After HCT-116 cells were treated with cadmium,the changes in cell malignant biological behavior were assessed by MTT assay,colony forming assay,cell adhesion assay,and transwell migration and invasion assays.Western blot was used to detect the expression of E-cadherin,Vimentin,Zinc finger E-box binding homeoboxl,MMP-3,MMP-9 and other proteins in cadmium treated cells.RESULTS Chronic exposure to cadmium enhanced the malignant biological behavior of HCT-116 cells,and the transformed cells formed mesenchymallike intercellular junctions.The protein expression of vimentin,MMP3,and MMP9 was increased,while the expression of E-cadherin was decreased in a time-dependent manner.Overall,morphological and molecular changes suggested that HCT-116 cells underwent an epithelial-mesenchymal transition（EMT）process after chronic cadmium exposure.CONCLUSION Cadmium enhances the malignant biologic behavior of HCT-116 cells possibly by inducing EMT.

关 键 词：镉 结直肠癌 上皮-间质转化 钙黏附蛋白E 波形蛋白 

分 类 号：R735.35[医药卫生—肿瘤]