MKP1对他莫昔芬耐药MCF7细胞耐药性的影响研究  

Effects of MKP1 on the drug sensitivity of tamoxifen resistant MCF7 cells

作　　者：白静静[1] 马刚 何建军[2] 潘怡霞 Ma Gang;He Jianjun;Bai Jingjing(Shaanxi Provincial Peopled Hospital,Xi'an 710068)

机构地区：[1]陕西省人民医院,西安710068 [2]西安交通大学医学部,西安710061

出　　处：《陕西医学杂志》2017年第11期1508-1512,共5页Shaanxi Medical Journal

基　　金：陕西省科技攻关项目(2011K13-01-08)

摘　　要：目的:研究MKP1对他莫昔芬耐药MCF7细胞耐药性的影响及其分子机制。方法:应用Real-time PCR和Western blot分析MKP1在MCF7和他莫昔芬耐药MCF7细胞中的表达变化;Western blot分析MKP1siRNA在他莫昔芬耐药MCF7细胞中对他莫昔芬诱导MAPK成员活化的影响;MTT比色法分析细胞活力;流式细胞仪分析细胞凋亡;SP600125抑制JNK活化。结果:与MCF7细胞相比,MKP1在他莫昔芬耐药MCF7细胞中表达上调;MKP1siRNA可增加他莫昔芬对耐药MCF7细胞活力的抑制作用;MKP1siRNA组与对照组相比,他莫昔芬介导的耐药MCF7细胞的凋亡显著增加;siRNA组与对照组相比,他莫昔芬诱导的JNK活化显著增强;SP600125抑制JNK活化后,MKP1siRNA组他莫昔芬耐药MCF7对他莫昔芬的耐药性部分恢复。结论:MKP1通过抑制他莫昔芬诱导的JNK活化维持MCF7他莫昔芬耐药细胞对他莫昔芬的耐药性。Objective:To investigate the effects of mitogen-activated protein kinase phosphatase l(M K P-l)on the drug sensitivity of tamoxifen resistance breast cancer MCF7cells and the molecular mechanisms.Methods:The expression of MKP1in MCF7and tamoxifen resistant MCF7cells were analyzed by Real-time PCR and Western Blot.Effects of MKP1siRNA on the activation of MAPKs mediated by tamoxifen in tamoxifen resistant MCF7cells were analyzed by Western Blot.M T T assy was used to analyze the effects of MKP1siRNA on survival rate of tamoxifen resistant MCF7cells after tamxoifen treatment.The effects of MKP1siRNA on apoptosis induced by tamoxifen in tamoxifen resistant MCF7cells were analyzed with flow cytometer.JNK inhibitor SP600125was used to treat MKP1siRNA group cells.Results:MKP1expression level was higher in tamoxifen resistant MCF7cells compared with parental MCF7cells.MKP1siRNA enhanced the tamoxifen sensitivity of tamoxifen resistant MCF7cells,and promoted the apoptosis induced by tamoxifen.Tamoxifen-induced activation of JNK significantly increased in MKP1siRNA group tamoxifen resistant MCF7cells compared with control group cells.SP600125recovered tamoxifen resistant capacity in MKP1siRNA group tamoxifen resistant MCF7cells.Conclusion:MKP1maintains tamoxifen resistant capacity in tamoxifen reisistant MCF7cells through blocking JNK activation.

关 键 词：药物耐受性 丝裂原活化蛋白激酶磷酸酶 他莫音芬 @MCF7 细胞凋亡 

分 类 号：R392.5[医药卫生—免疫学]