罗格列酮对耐药乳腺癌细胞影响的研究  

Effects of rosiglitazone on the drug-resistant breast cancer

作　　者：陈皖京 汤铜[1] 钱波[1] 李佳[1] 田多[1] 郑璐[1] 

机构地区：[1]安徽医科大学第二附属医院普通外科,合肥230601

出　　处：《安徽医科大学学报》2015年第3期285-289,共5页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金项目(编号:1308085QH152)

摘　　要：目的探讨罗格列酮(ROS)对耐他莫西芬(TAM)的乳腺癌细胞MCF-7/TAM体外生长的影响,及对其耐药性的逆转效果和作用机制。方法采用四甲基偶氮唑蓝(MTT)比色分析法测定ROS作用于MCF-7/TAM细胞后的抑制率及逆转耐药的效果;采用流式细胞术检测ROS作用MCF-7/TAM细胞后的凋亡率;采用实时定量荧光PCR技术检测ROS作用MCF-7/TAM细胞后对FOXA1、ERα、Erb B-2和P53基因表达的影响。结果 ROS干预MCF-7/TAM细胞后,呈量-效和时-效关系抑制其增殖。半数抑制浓度(136μmol/L)的ROS对MCF-7/TAM细胞具有明显的逆转耐药效果,逆转耐药倍数为2.05倍。高浓度可诱导MCF-7/TAM细胞凋亡。半数抑制浓度(136μmol/L)的ROS作用MCF-7/TAM细胞后,能够上调FOXA1、ERα和P53基因表达水平(P<0.05),下调Erb B-2基因表达水平(P<0.05)。结论ROS可抑制MCF-7/TAM细胞增殖,高浓度ROS可诱导其凋亡,其机制可能与上调P53基因表达有关。ROS可逆转MCF-7/TAM细胞的耐药性,逆转机制可能与上调FOXA1和ERα基因表达,下调Erb B-2基因表达有关。Objective To investigate the proliferation inhibition and the reverse effects as well as the mechanisms of rosiglitazone（ ROS） on human breast cancer cells resistant to tamoxifen（ MCF-7/TAM） in vitro. Methods The inhibitive rate and reverse effects of ROS on MCF-7/TAM cells were detected by MTT assay. The apoptotic rate of ROS on MCF-7/TAM cells were detected by flow cytometry. The expression changes of FOXA1,ERα,ErbB-2 and P53 of MCF-7/TAM cells which dealed with ROS were detected by real-time quantitative PCR. Results ROS could inhibit the proliferations of MCF-7/TAM cells through dose-effect and time-effect relationships. ROS had a significant reversal of drug resistance of MCF-7/TAM cells. The dose of 50% inhibitory concentration（136 μmol/L） reversed the resistance by 2. 05 folds. High concentration of ROS could induce the MCF-7/TAM cells apoptosis. The expressions of FOXA1,ERα and P53 were increased after ROS effected on MCF-7/TAM cells at the dose of 50% inhibitory concentration（136 μmol/L） （P 〈0. 05）. While,the expressions of ErbB-2 were induced by ROS with the same concentration（P 〈0. 05）. Conclusion The effects of proliferation inhibition and apoptosis of ROS on MCF-7/TAM cells may be related to down-regulating P53 expression. ROS can reverse the drug resistance of MCF-7/TAM cells,and the reverse mechanisms maybe relate to up-regulating FOXA1 and ERα expression as well as down-regulating ErbB-2 .

关 键 词：罗格列酮 他莫西芬 乳腺癌细胞 FOXA1 ERΑ ERBB-2 P53 

分 类 号：R737.9[医药卫生—肿瘤]