自噬
PI3K/AKT/mTOR通路
榄香烯
ATG5型
活力测定
细胞凋亡
蛋白激酶B
A549电池
流式细胞术
细胞生物学
化学
癌症研究
生物
分子生物学
生物化学
作者
Jing Liu,Xuejun Hu,Bo Jin,Xiujuan Qu,Kezuo Hou,Yunpeng Liu
标识
DOI:10.1111/j.2042-7158.2011.01371.x
摘要
Abstract Objectives β-Elemene, a novel traditional Chinese medicine, has been shown to be effective against a wide range of tumours. In this study, the antitumour effect of β-elemene on human non-small-cell lung cancer (NSCLC) A549 cells and the mechanism involved have been investigated. Methods Cell viability and apoptosis were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Protein expression was assayed by Western blotting. Autophagy was evaluated under fluorescence microscopy and transmission electron microscopy. Key findings β-Elemene inhibited the viability of A549 cells in a dose-dependent manner. This suppression of cell viability was due to the induction of apoptosis. Further study showed that β-elemene inhibited the activity of the PI3K/Akt/mTOR/p70S6K1 signalling pathway, and at the same time it triggered a robust autophagy. The autophagy was characterized by the accumulation of punctate LC3 dots in the cytoplasm, morphological changes, and the increased levels of LC3-II as well as Atg5-Atg12 conjugated proteins. Inhibition of autophagy with chlorochine significantly enhanced the antitumour effect of β-elemene. Conclusions Our data indicated that β-elemene inhibited the activity of the PI3K/Akt/mTOR/p70S6K1 signalling pathway in human NSCLC A549 cells, which resulted in apoptosis as well as protective autophagy. A combination of β-elemene with autophagy inhibitor might be an effective therapeutic option for advanced NSCLC.
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