南方医科大学学报2019，Vol.39Issue(2)：162-168,7.DOI:10.12122/j.issn.1673-4254.2019.09.06
自噬相关基因3过表达促进乳腺癌细胞自噬并抑制盐霉素诱导的细胞凋亡
Overexpression of autophagy-related gene 3 promotes autophagy and inhibits salinomycin-induced apoptosis in breast cancer MCF-7 cells
摘要
Abstract
Objective To study the effects of the overexpression of autophagy-related gene 3 (ATG3) on autophagy and salinomycin-induced apoptosis in breast cancer cells and explore the underlying mechanisms.Methods We used the lentivirus approach to establish a breast cancer cell line with stable overexpression of ATG3.Western blotting, immunofluorescence staining and transmission electron microscopy were used to analyze the effect of ATG3 overexpression on autophagy in breast cancer MCF-7 cells.Using the AKT/mTOR agonists SC79 and MHY1485, we analyzed the effect of AKT/mTOR signal pathway activation on ATG3 overexpression-induced autophagy.Western blotting and flow cytometry were used to analyze the effect of autophagy on apoptosis of the ATG3-overexpressing cells treated with salinomycin and 3-MA (an autophagy inhibitor).Results In ATG3-overexpressing MCF-7 cells, ATG3 overexpression obviously promoted autophagy, inhibited the AKT/mTOR signaling pathway, significantly weakened salinomycin-induced apoptosis (P＜0.01), caused significant reduction of the levels of the pro-apoptotic proteins cleaved-caspase 3 (P＜0.01) and Bax (P＜0.05), and enhanced the expression of the anti-apoptotic protein Bcl-2 (P＜0.05).The inhibition of autophagy obviously weakened the inhibitory effect of ATG3 overexpression on salinomycin-induced apoptosis.Conclusion ATG3 overexpression promotes autophagy possibly by inhibiting the AKT/mTOR signaling pathway to decrease salinomycin-induced apoptosis in MCF-7 cells, suggesting that autophagy induction might be one of the mechanisms of drug resistance in breast cancer cells.关键词
自噬相关基因3/慢病毒/细胞自噬/盐霉素/乳腺癌Key words
autophagy-related gene 3/lentivirus/autophagy/salinomycin/breast cancer引用本文复制引用
李芳,黄果,彭平,刘瑶,李双辉,刘罗根,章运生..自噬相关基因3过表达促进乳腺癌细胞自噬并抑制盐霉素诱导的细胞凋亡[J].南方医科大学学报,2019,39(2):162-168,7.基金项目
湖南省自然科学基金 (2018JJ3462) （2018JJ3462）
湖南省卫生健康委科研计划 (B2019107) （B2019107）
