Celastrol Triggers Autophagy in Human Cervical Cancer Hela Cells in Vitro and in Vivo
- Author:
Na LI
1
Author Information
- Publication Type:Journal Article
- Keywords: Akt; Autophagy; Celastrol; Cell cycle; Cervical carcinoma
- From: Chinese Pharmaceutical Journal 2018;53(7):513-517
- CountryChina
- Language:Chinese
- 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 Ⅱ 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 Ⅱ 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.
