沙利霉素诱导的自噬通过 ATG3/AKT/mTOR 信号通路在 PC-3 细胞中阻断细胞凋亡。
Salinomycin-induced autophagy blocks apoptosis via the ATG3/AKT/mTOR signaling axis in PC-3 cells.
机构信息
Clinical Research Institute, The Second Affiliated Hospital, University of South China, Hengyang 421001, PR China.
College of Nursing, Hunan Polytechnic of Environment and Biology, Hengyang 421005, PR China.
出版信息
Life Sci. 2018 Aug 15;207:451-460. doi: 10.1016/j.lfs.2018.06.034. Epub 2018 Jun 30.
AIMS
This study evaluated the mechanism by which salinomycin-induced autophagy blocks apoptosis in PC-3 prostate cancer cells.
MAIN METHODS
The anti-cancer effects of salinomycin in PC-3 cells were confirmed by flow cytometry, JC-1 staining and western blotting. Then, the autophagic effects were measured by western blotting, GFP-LC3 puncta formation assay, immunofluorescence staining and electron microscopy. Furthermore, we used lentivirus-mediated shRNA to silence ATG3, ATG5 and ATG7 expression in PC-3 cells to investigate the regulatory mechanisms of salinomycin-induced autophagy.
KEY FINDINGS
Salinomycin could induce apoptosis and autophagy in PC-3 cells. Interestingly, autophagy inhibition could enhance salinomycin-induced apoptosis. We further showed that ATG3, a known critical regulator of autophagy, was downregulated and involved in the inhibition of apoptosis by salinomycin-induced autophagy via the AKT/mTOR signaling axis.
SIGNIFICANCE
Our data indicated that salinomycin-induced autophagy blocks apoptosis via the ATG3/AKT/mTOR signaling axis in PC-3 cells, which provides new clues for the mechanisms of underlying the anti-cancer effects of salinomycin.
目的
本研究旨在评估盐霉素诱导自噬阻止 PC-3 前列腺癌细胞凋亡的机制。
方法
通过流式细胞术、JC-1 染色和 Western blot 验证盐霉素对 PC-3 细胞的抗癌作用。然后，通过 Western blot、GFP-LC3 斑点形成试验、免疫荧光染色和电子显微镜测量自噬作用。此外，我们使用慢病毒介导的 shRNA 沉默 PC-3 细胞中的 ATG3、ATG5 和 ATG7 表达，以研究盐霉素诱导自噬的调控机制。
主要发现
盐霉素可诱导 PC-3 细胞凋亡和自噬。有趣的是，自噬抑制可增强盐霉素诱导的细胞凋亡。我们进一步表明，ATG3 是自噬的已知关键调节因子，通过 AKT/mTOR 信号通路下调并参与盐霉素诱导自噬对细胞凋亡的抑制。
意义
我们的数据表明，盐霉素诱导的自噬通过 ATG3/AKT/mTOR 信号轴阻止 PC-3 细胞中的细胞凋亡，为盐霉素抗癌作用的机制提供了新的线索。
Zotero 插件