c-Met对三阴性乳腺癌细胞增殖及阿霉素耐药性的影响  

Effects of c-Met on proliferation of triple negative breast cancer and sensitivity to doxorubicin

作　　者：邓智平[1,2] 廖和和[1] 王周权[1] 杨波[1] 宋张骏[1] 姚俊涛[1] 任宏[1] 张明鑫[3] 

机构地区：[1]西安交通大学医学院第一附属医院胸外二科,陕西西安710061 [2]陕西省肿瘤医院乳腺科,陕西西安710061 [3]第四军医大学唐都医院,陕西西安710000

出　　处：《中国病理生理杂志》2015年第3期447-451,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81302055);陕西省自然科学基金资助项目(No.2013JM4035)

摘　　要：目的:研究c-Met对三阴性乳腺癌细胞株MDA-MB-231活力及对阿霉素耐药性的影响。方法:构建阿霉素耐药的MDA-MB-231/ADR细胞系,实时荧光定量PCR及Western blotting技术检测不同细胞系中c-Met mRNA及蛋白的表达。脂质体转染c-Met-siRNA及表达质粒或AKT-siRNA,Western blotting检测转染效率;四甲基偶氮唑法(MTT法)检测细胞的活力及对阿霉素的敏感性。结果:对阿霉素耐药的MDA-MB-231/ADR细胞中cMet的mRNA及蛋白表达均显著高于对照的MDA-MB-231细胞,转染高表达c-Met的质粒可增加MDA-MB-231细胞的活力并降低其对阿霉素的敏感性,而利用siRNA抑制耐药细胞株中c-Met的表达后,可以逆转MDA-MB-231/ADR细胞对阿霉素的耐药。此外,c-Met可以磷酸化激活细胞中的AKT,并通过该信号分子增加MDA-MB-231细胞活力并诱导耐药。结论:c-Met可作为一个重要的靶点应用于三阴性乳腺癌的治疗。AIM：To investigate the effects of c-Met on the proliferation and the sensitivity to chemotherapeutic drugs of triple negative breast cancer cells.METHODS： Doxorubicin-resistant cells （ MDA-MB-231/ADR） were estab-lished.The expression of c-Met at mRNA and protein levels in the MDA-MB-231/ADR cells and parental MDA-MB-231 cells was detected by real-time PCR and Western blotting.c-Met siRNA and plasmid or AKT siRNA were transfected into the cancer cells.The cell proliferation and the sensitivity to doxorubicin were determined by MTT assay.RESULTS：The expression of c-Met at mRNA and protein levels in MDA-MB-231/ADR cells was significantly higher than that in parental MDA-MB-231 cells.Transfection with pBABE-puro TPR-MET plasmid into the MDA-MB-231 cells induced cell prolifera-tion and resistance to doxorubicin.Meanwhile, inhibition of c-Met in the MDA-MB-231/ADR cells by siRNA reversed the doxorubicin-resistance.In addition, over-expression of c-Met led to higher phosphorylation level of AKT, which was in-volved in the effects of c-Met on the MDA-MB-231 cell proliferation and doxorubicin-resistance.CONCLUSION： c-Met may have the potential as a therapeutic target in the treatment of triple negative breast cancer.

关 键 词：C-MET 三阴性乳腺癌 细胞增殖 阿霉素 耐药性 

分 类 号：R363[医药卫生—病理学] R737.9[医药卫生—基础医学]