STAT3基因沉默对乳腺癌阿霉素耐药性的影响  

Effect of STAT3 knockdownon the sensitivity of breast cancer cells to adriamycin

作　　者：全军利 贺文兴[1] 吴斯敏[1] 李健林[1] 刘志明[1] 

机构地区：[1]广西医科大学第一附属医院胃肠腺体外科

出　　处：《实用医学杂志》2015年第11期1748-1751,共4页The Journal of Practical Medicine

基　　金：2014年广西研究生教育创新计划资助项目(编号:YCSZ2014115)

摘　　要：目的:观察STAT3短发夹RNA慢病毒载体(LV-sh RNA-STAT3)对乳腺癌耐药株MCF-7/ADR阿霉素敏感性的影响。方法:Western blot检测MCF-7/ADR及亲本细胞MCF-7中STAT3和p-STAT3蛋白表达;LVsh RNA-STAT3感染MCF-7/ADR(STAT3-RNAi组),同时感染无义序列Scramble-sh RNA作为阴性对照(NC组),空白组不作处理(Con组),荧光显微镜观察转染效率,q RT-PCR及Western blot检测STAT3 m RNA和蛋白、p-STAT3蛋白表达;不同浓度阿霉素处理各组细胞48h,MTT法检测细胞生长抑制率;流式细胞术检测细胞凋亡率。结果:STAT3、p-STAT3蛋白在MCF-7/ADR中表达较MCF-7增强(P<0.05);STAT3-RNAi组STAT3 m RNA和蛋白、p-STAT3蛋白表达与Con组、NC组比较明显减弱,差异具有统计学意义(P<0.05);阿霉素对Con组、NC组和STAT3-RNAi组细胞的IC50分别为(56.1±3.00)μg/m L、(54.9±11.9)μg/m L和(7.6±0.2)μg/m L;Con组、NC组和STAT3-RNAi组的细胞凋亡率分别为(10.5±0.7)%、(11.7±0.7)%和(34.0±3.1)%。结论 :LVsh RNA-STAT3可显著抑制STAT3基因表达,有效增强乳腺癌对阿霉素的敏感性,其机制与促进细胞凋亡有关。Objective To investigate the effect of STAT3 knockdown on the sensitivity of breast cancer cells with drug-resistant to adriamycin （MCF-7/ADR）. Methods Levels of STAT3 and p-STAT3 in MCF-7/ ADR and MCF-7 cells were detected by Western Blot. The MCF-7/ADR cells were infected with lentivirus expressing STAT3-shRNA and the negative control vectors in the STAT3-RNAi group and NC group, respectively, wihle the cells in the blank group received no treatment. The transfection efficiency was observed with fluorescence microscope, the mRNA level of STAT3, protein levels of STAT3 and p-STAT3 were detected by qRT-PCR and Western Blot, respectively. MCF-7/ADR cells were treated with different concentrations of adriamyein for 48 hours, cell proliferation was detected by MTF assay and cell apoptosis was detected by flow cytometry. Results Levels of STAT3 and p-STAT3 in MCF-7/ADR cells were significantly higher than those in the MCF-7 cells （P 〈 0.05）. The levels of STAT3 mRNA, STAT3 and p-STAT3 in the STAT3-RNAi group were significantly lower than those in the Con group and the NC group （P 〈 0.05, respectively）. The Adriamycin ICs0 in the Con group, NC group and STAT3-RNAi group was （56.1±3.00）ug/mL, （54.9±11.9）ug/mL and （7.6±0.2）ug/mL, respectively. The flow cytometry results showed that the cell apoptosis in the Con group, the NC group and the STAT3-RNAi group was （10.5±0.7）%, （11.7±0.7）% and （34±3.1）%, respectively. Conclusion LV-shRNA-STAT3 can significantly inhibit STAT3 expression and enhance the sensitivity of breast cancer cells to adriamycin, and the underlying mechanism may be related to cell apoptosis.

关 键 词：乳腺肿瘤 STAT3 阿霉素 化疗敏感性 

分 类 号：R737.9[医药卫生—肿瘤]