TEP-10对乳腺癌MCF-7/ADR细胞耐药作用的影响及其机制研究  

Effect of TEP-10 on Multidrug Resistance of MCF-7/ADR Cells in Breast Cancer and Its Mechanism

作　　者：郑凯音 郭宏举 张捷[1] 史宁[1] 吴久鸿[1] ZHENG Kai-yin;GUO Hong-ju;ZHANG Jie;SHI Ning;WU Jiu-hong(Department of Pharmacy,980 Hospital of PLA Joint Logistics Support Forces,Shijiazhuang 050082,China)

机构地区：[1]中国人民解放军联勤保障部队第九八〇(白求恩国际和平)医院药剂科

出　　处：《解放军医药杂志》2019年第6期15-19,共5页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：国家自然科学基金资助项目(81470156)

摘　　要：目的探究TEP-10对阿霉素(ADR)耐药乳腺癌MCF-7/ADR细胞多药耐药性(MDR)作用的影响及其机制。方法体外培养非耐药乳腺癌MCF-7细胞及耐药乳腺癌MCF-7/ADR细胞,通过MTT法检测不同浓度TEP-10及TEP-10IC20浓度下ADR对2种乳腺癌细胞增殖抑制效果并计算药物相互作用指数;流式细胞术和激光共聚焦显微镜观察TEP-10对罗丹明123外泵能力的影响;通过检测MDR1基因、P-gp蛋白的表达探究其初步机制。结果MCF-7/ADR细胞药物相互作用指数小于MCF-7细胞。20μg/ml的TEP-10预处理可显著增加MCF-7/ADR细胞罗丹明123的荧光强度。5μg/ml、10μg/ml和20μg/ml的TEP-10能显著下调MCF-7/ADR细胞MDR1基因mRNA和P-gp蛋白的表达(P<0.05,P<0.01)。结论TEP-10通过下调MCF-7/ADR细胞MDR1基因的转录翻译,增加胞内抗癌药物蓄积从而逆转MCF-7/ADR细胞的MDR。Objective To investigate effect of TEP-10 on multidrug resistance (MDR) of MCF-7/Adriamycin (MCF-7/ADR) cells in breast cancer and its mechanism. Methods Non- resistance MCF-7 and MCF-7/ADR cells were cultured in vitro. ADR effects on proliferation and inhibition of two kinds of breast cancer cells with different concentrations of TEP-10 and TEP-10 IC 20 treatment were determined by MTT assay, and coefficient of drug interaction (CDI) was calculated. Flow cytometry and confocal laser microscope were used to observe effect of TEP-10 on intracellular accumulation of Rhodamine 123. Preliminary mechanism was studied by detecting MDR1 gene and P-gp protein expressions. Results Value of TEP-10 CDI in MCF-7/ADR cells was less than that in MCF-7 cells. Pretreatment with 20μg/ml TEP-10 could significantly increase fluorescence intensity of Rhodamine 123 in MCF-7/ADR cells. The 5μg/ml, 10μg/ml and 20μg/ml TEP-10 significantly reduced MDR1 gene mRNA and P-gp protein expressions in MCF-7/ADR cells ( P < 0.05, P <0.01). Conclusion TEP-10 may reverse MDR of MCF-7/ADR cells by reducing transcription and translation of MDR1 gene in MCF-7/ADR cells and increasing intracellular accumulation of anti-cancer drugs.

关 键 词：乳腺肿瘤 TEP-10 抗药性 肿瘤 

分 类 号：R737.9[医药卫生—肿瘤]