文章摘要

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

作者: 1吴 至佛, 1姚 晓艺, 1汪 灵, 1邓 增艳, 1石 静, 1黄 俊辉
1 中南大学湘雅医院 肿瘤科,湖南 长沙 410008
通讯: 黄 俊辉 Email: 808003@csu.edu.com
DOI: 10.3978/.2018.06.012
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(IC25);用 IC25 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 IC25 为 3.11 μg/mL。IC25 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。
关键词: 三阴性乳腺癌;抗药性,肿瘤;自噬;细胞凋亡

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

Authors: 1WU Zhifo, 1YAO Xiaoyi, 1WANG Ling, 1DENG Zengyan, 1SHI Jing, 1HUANG Junhui
1 Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, China

CorrespondingAuthor:HUANG Junhui Email: 808003@csu.edu.com

Abstract

Objective: To investigate the infl uence of paclitaxel on expression of autophagy-associated protein LC3 in triple negative breast cancer (TNBC) cells and the signifi cance.
Methods: Th e inhibitory eff ect 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 aft er treatment with IC25 concentration of paclitaxel, the expressions of LC3 protein and apoptosis-associated proteins as well as the cell apoptosis rates were determined by immunofl uorescence histochemistry, Western blot analysis and fl ow 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 after treatment 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.
Keywords: Triple Negative Breast Neoplasms; Drug Resistance Neoplasm; Autophagy; Apoptosis