Autophagy inhibition facilitates the anti-proliferative effect of pemetrexed on A549 cells
10.3969/j.issn.1001-1978.2015.05.015
- VernacularTitle:抑制自噬促进培美曲塞对A549细胞的增殖抑制作用
- Author:
Dahai ZHAO
;
Youjin LU
- Publication Type:Journal Article
- Keywords:
autophagy;
pemetrexed;
lung cancer;
LC3;
p62;
chloroquine
- From:
Chinese Pharmacological Bulletin
2015;(5):664-667,668
- CountryChina
- Language:Chinese
-
Abstract:
Aim To explore the effect of pemetrexed on autophagy and the function of autohpagy activation in A549 cells.Methods The anti-proliferative effect of pemetrexed on A549 cells was detected by MTS. The formation of autophagosome was observed by trans-mission electron microscopy (TEM)and the expression of autophagy-related proteins was determined by West-ern blot.The inhibitory effects of the combination of pemetrexed and a selective autophagy inhibitor on A549 cells were measured by MTS.Results Peme-trexed inhibited the proliferation of A549 cells.Auto-phagy was activated in A549 cells by exposure to pemtrexed.Autophagosome was increased in peme-trexed treatment cells compared with control group. Pemtrexed treatment led to the formation of autophago-some and the conversion of LC3-Ⅰto LC3-Ⅱ.The in-crease of Beclin-1 and the decline of autophagy sub-strate of p62 were observed in pemtrexed treated A549 cells.The pharmacological autophagy inhibitor chloro-quine (CQ)sensitized A549 cells to pemetrexed treat-ment.The inhibitory rate was (28.42 ±2.45 )% for pemetrexed only,and (45 .36 ±3.52 )% for peme-trexed combined with CQ.Conclusions Pemetrexed could activate autophagy in A549 cell lines.The dis-ruption of autophagy facilitates the anti-proliferative effect of pemetrexed on A549 cells,which provides a novel strategy in lung cancer treatment.
