ERK抑制剂U0126通过下调cyclin D1与survivin蛋白表达抑制乳腺癌细胞增殖  

Inhibition of proliferation of breast cancer cells by down-regulation of cyclin D1 and survivin protein expression by ERK inhibitor U0126

作　　者：田继华[1] 常思佳 郭海秀[1] 冀贺 王艳红[1] TIAN Ji-hua;CHANG Si-jia;GUO Hai-xiu;JI He;WANG Yan-hong(Dept of Microbiology and Immunology,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学微生物学与免疫学教研室

出　　处：《中国药理学通报》2019年第8期1061-1066,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金青年基金项目(No 81500529,81500518);山西医科大学博士启动基金(No 03201403)

摘　　要：目的 研究ERK通路抑制剂U0126对乳腺癌细胞增殖的抑制作用,并探讨其调控机制。方法培养人乳腺癌细胞株MCF-7、MDA-MB231,将细胞分组干预,MTT法检测各组细胞增殖情况;流式细胞仪检测各组细胞周期及细胞凋亡;Western blot检测细胞中p-ERK/ERK、cyclin D1、survivin及cleaved caspase-3蛋白表达。结果 MTT结果显示,U0126干预24、48 h后,MCF-7、MDA-MB231细胞抑制率明显增加(P<0.01);MCF-7、MDA-MB231细胞经U0126干预24 h后,检测细胞周期及细胞凋亡,G 0/G 1期细胞比例较对照组明显增加,S及G 2期细胞比例下降(P<0.05);而干预组细胞凋亡率较未干预组明显增多(P<0.01);U0126处理人乳腺癌细胞2 h后,可阻断ERK的磷酸化,减少cyclin D1的蛋白表达,抑制survivin而上调cleaved caspase-3的表达,与对照组相比差异有显著性(P<0.01)。结论 U0126通过阻断MCF-7、MDA-MB231细胞中ERK信号通路,调控cyclin D1,将细胞周期阻断在G 0/G 1期,抑制survivin而增加cleaved caspase-3表达,增加细胞凋亡,继而使乳腺癌细胞MDA-MB231、MCF-7的增殖受到抑制。Aim To investigate the inhibitory effect of ERK signaling pathway inhibitor UO126 on breast cancer cell proliferation and explore its specific regulatory mechanism.Methods Cultured human breast cancer cell MCF-7,MDA-MB231,the cell were divided into different groups and intervened.MTT was used to measure the cell proliferation;Flow cytometry was employed to test cell cycle and cell apoptosis;Western blot was applied to test p-ERK/ERK,cyclin D1,survivin and cleaved caspase-3 protein expression.Results The results of MTT showed that the inhibitory rate of MCF-7 and MDA-MB231 cells increased significantly after U0126 intervention for 24 h and 48 h(P<0.01).Cell cycle and apoptosis were detected by MCF-7 and MDA-MB231 cells treated with U0126 for 24 h.The proportion of cells in G 0/G 1 phase was significantly higher than that in control group,and the proportion of cells in S and G 2 phase decreased(P<0.05).The apoptotic rate in intervention group was significantly higher than that in non-intervention group,and the difference was significant(P< 0.01);U0126 treatment of human breast cancer cells could block ERK phosphorylation,increase cyclin D1 protein expression,inhibit survivin and up-regulate cleaved caspase3 expression,which were significantly different from control group(P<0.05).Conclusions U0126 blocks ERK signaling pathway in MCF-7,MDA-MB231,down-regulates the cyclin D1,and blocks cell cycle in G 0/G 1 phase,then it inhibits the expression of survivin and increases cleaved caspase-3,promotes cell apoptosis,and inhibits the proliferation of breast cancer cell MCF-7,MDA-MB231.

关 键 词：ERK U0126 MCF-7 MDA-MB231 CYCLIN D1 SURVIVIN 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学] R329.25[医药卫生—基础医学]