Celastrol induces cell cycle arrest by MicroRNA-21-mTOR-mediated inhibition p27 protein degradation in gastric cancer.
OBJECTIVE
Celastrol has anti-cancer effects by increase of apoptosis of gastric cancer cells. However, its role in gastric cancer cell cycle is still unclear. The aim of this study was to investigate the effect and mechanism of celastrol on gastric cancer cell cycle.


METHODS
The effects of celastrol on cell cycle in BGC-823 and MGC-803 cells were assayed via flow cytometry analysis. The expression of p27 and mTOR was detected by real-time PCR and western blot. The activity of mTOR and mTORC2 was measured by mTOR and mTORC2 kinase assays. miR-21 mimic was used to up-regulate miR-21 expression and mTOR expression plasmid was used to increase mTOR level in gastric cancer cells.


RESULTS
Celastrol caused G2/M cell-cycle arrest that was accompanied by the down-regulation of miR-21 expression. In particular, miR-21 overexpression reversed cell cycle arrest effects of celastrol. Further study showed that celastrol increased levels of the p27 protein by inhibiting its degradation. miR-21 and mTOR signaling pathway was involved in the increase of p27 protein expression in BGC-823 and MGC-803 cells treated with celastrol. Significantly, miR-21 overexpression restored the decrease of mTOR activity in cells exposed celastrol.


CONCLUSIONS
The effect of celastrol on cell cycle arrest of gastric cancer cells was due to an increase of p27 protein level via inhibiting miR-21-mTOR signaling pathway.
Institute of Clinical Medicine, Taizhou People's Hospital Affiliated of Nantong University of Medicine, Taizhou, 225300 China.
Min
M
Sha
Institute of Clinical Medicine, Taizhou People's Hospital Affiliated of Nantong University of Medicine, Taizhou, 225300 China.
Jun
J
Ye
Institute of Clinical Medicine, Taizhou People's Hospital Affiliated of Nantong University of Medicine, Taizhou, 225300 China.
Zheng-Yun
ZY
Luan
Institute of Clinical Medicine, Taizhou People's Hospital Affiliated of Nantong University of Medicine, Taizhou, 225300 China.
Ting
T
Guo
Institute of Clinical Medicine, Taizhou People's Hospital Affiliated of Nantong University of Medicine, Taizhou, 225300 China.
Bian
B
Wang
Institute of Oncology, Taizhou People's Hospital Affiliated of Nantong University of Medicine, 210 Yingchun, Taizhou, 225300 Jiangsu China.
Jun-Xing
JX
Huang
Celastrol; Cell cycle arrest; mTOR; miR-21; p27