期刊
LIFE SCIENCES
卷 207, 期 -, 页码 451-460出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2018.06.034
关键词
Salinomycin; Autophagy; ATG3/AKT/mTOR signaling axis; PC-3 cells
资金
- National Natural Science Foundation of China [81241090, 81372378]
- Natural Science Foundation of Hunan Province [2018JJ3462, 2016WK2013]
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 down regulated 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.
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