Autophagy inhibition facilitates the anti-proliferative effect of pemetrexed on A549 cells / 中国药理学通报

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.