紫杉醇诱导三阴性乳腺癌细胞自噬相关蛋白LC3的表达及其作用  

Paclitaxel induced expression of autophagy-associated protein LC3 in triple negative breast cancer cells and its action

作　　者：吴至佛 姚晓艺[1] 汪灵[1] 邓增艳 石静[1] 黄俊辉[1] WU Zhifo;YAO Xiaoyi;WANG Ling;DENG Zengyan;SHI Jing;HUANG Junhu(Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, China)

机构地区：[1]中南大学湘雅医院肿瘤科,湖南长沙410008

出　　处：《中国普通外科杂志》2018年第6期732-739,共8页China Journal of General Surgery

基　　金：湖南省自然科学基金资助项目(11jj3122);中南大学研究生自主探索创新基金资助项目(2016zzts531)

摘　　要：目的:探讨紫杉醇对三阴性乳腺癌(TNBC)细胞自噬相关蛋白LC3表达的影响及意义。方法:用CCK-8法测定紫杉醇对TNBC细胞MDA-MB-231增殖的抑制作用及25%抑制浓度(IC_(25));用IC_(25)浓度的紫杉醇作用MDA-MB-231细胞后,分别用免疫荧光化学法、Western blot、流式细胞术检测细胞LC3与凋亡相关蛋白的表达及细胞的凋亡率。结果:紫杉醇呈浓度依懒性抑制MDA-MB-231细胞的增殖(P<0.05),其IC_(25)为3.11μg/m L。IC_(25)浓度的紫杉醇处理后,MDA-MB-231细胞后LC3的表达量以及LC3B/LC3A比例明显升高、凋亡蛋白Bax与caspase-3蛋白表达量明显降低、总凋亡率与早期调亡率均明降低(均P<0.05)。结论:紫杉醇可诱导TNBC细胞自噬相关蛋白LC3表达升高,该作用可能降低细胞凋亡,从而导致TNBC细胞产生紫杉醇耐药。Objective. To investigate the influence of paclitaxel on expression of autophagy-associated protein LC3 in triple negative breast cancer （TNBC） cells and the significance. Methods： The inhibitory effect of paclitaxel on proliferation of TNBC MDA-MB-231 cells was determined by CCK-8 assay and then the 25% inhibition concentration （IC25） value was calculated. In MDA-MB-231 cells after treatment with IC25 concentration ofpaclitaxel, the expressions of LC3 protein and apoptosis-associated proteins as well as the cell apoptosis rates were determined by immunofluorescence histochemistry, Western blot analysis and flow cytometry, respectively. Results： The proliferation effect of TNBC-MDA-MB-231 cells was significantly inhibited by paclitaxel in a concentration-dependent manner （P〈0.05）, with an IC25 value of 3.11 μg/mL. In MDA-MB-231 cells aftertreatment with 3.11 μg/mL paclitaxel, the expression level of LC3 protein as well as LC3B/LC3A ratio were significantly increased, the expression levels of the apoptosis-related protein Bax and caspase-3 were significantly decreased, and the total and early apoptosis rates were significantly decreased （all P〈0.05）. Conclusion： Paclitaxel can induce the increased expression of the autophagy-related protein LC3, and this action may probably reduce the cell apoptosis and thereby cause paclitaxel resistance in TNBC cells.

关 键 词：三阴性乳腺癌 抗药性 肿瘤 自噬 细胞凋亡 

分 类 号：R737.9[医药卫生—肿瘤]