Celastrol Triggers Autophagy in Human Cervical Cancer Hela Cells in Vitro and in Vivo
LI Na1, ZHANG Tian-dong1, WANG Yue-feng1, SHAN Yuan-yuan2
1. Department of Pharmacy, Xinxiang Central Hospital, Xinxiang 453000, China; 2. Department of Pharmacy, The First Affiliated Hospital of Xi��an Jiaotong University, Xi��an 710061, China
Abstract��OBJECTIVE To investigage the effects of celastrol-triggered HeLa cells autophagy and the molecular mechanisms in vitro and in vivo. METHODS The antiproliferative effect of celastrol was detected using MTT assay. Apoptotic rate and cell cycle were evaluated using flow cytometric analysis. Autophagy was detected using fluorescence microscope. Protein expression was evaluated using Western blotting. Tumor growth was evaluated by subcutaneous xenograft model in vivo. RESULTS Celastrol inhibited HeLa cells proliferation and induced HeLa cells autophagy and cell cycle arrest at G0/G1 phase, but not induced HeLa cell apoptosis in vitro. The protein expression of Beclin 1 was up-regulated and the conversion from LC3 �� to LC3 �� was increase in HeLa cells in vitro after treatment with celastrol. Moreover, celastrol promoted the protein expression of PTEN��p-ERK1/2��p-MEK1/2 and inhibited the phosphorylated of Akt, p70S6K and mTOR in HeLa cells. After pretreatment with 3-methyladenine (5 mmol��L-1), the antiproliferative and induced-autophagy effects of celastrol were reversed. Furthermore, celastrol inhibited tumor growth and the protein expression of p-Akt and p-mTOR, but up-regulated the protein expression of LC3 �� and Beclin 1 in vivo. CONCLUSION Antitumor effect of celastrol dependent on cells autophagy in HeLa cells via inhibition of Akt/mTOR signaling pathway in vitro and in vivo.
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LI Na, ZHANG Tian-dong, WANG Yue-feng, SHAN Yuan-yuan. Celastrol Triggers Autophagy in Human Cervical Cancer Hela Cells in Vitro and in Vivo. Chinese Pharmaceutical Journal, 2018, 53(7): 513-517.
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