基础医学与临床2017,Vol.37Issue(2):176-182,7.
顺铂对膀胱癌细胞自噬和凋亡的作用及其相关性
Effects of cisplatin on autophagy and apoptosis and their correlation in bladder cancer cells
摘要
Abstract
Objective To identify whether cisplatin can induce autophagy of bladder cancer T24 cells and the possible mechanism, and to observe the relationship between outophagy and apoptosis.Methods MTT assay was applied to investigate the effects of various concentration of cisplatin( 0 , 10 , 20 and 40 μg/mL) on T24 survival.TEM was performed to detect the autophagosome formation .Western blot assay was used to analyze the expression changes of LC3-Ⅱ, P62 and extracellular signal-regulated kinase ( ERK1/2 ) and p-ERK at the protein level.The effects of autophagy on the survival and apoptosis of bladder cancer cells were investiga-ted.Results DDP observably inhibited proliferation of bladder cancer cells in a dose-dependent manner ( P<0.05), the 50% inhibiting concentration(IC50) was (30.3 ±2.4)μg/mL;DDP induced autophagy of bladder cancer cells, observably increased autophagosome induced by DDP; up-regulated expression levels of LC3-Ⅱproteins ( P<0.05 ) , down-regulated expression of P62 proteins ( P<0.05 );DDP increased the protein level of p-ERK (P<0.05); The inhibitor of ERK pathway U0126 inhibited DDP-induced autophagy, as evidenced by decrease in the expression of LC3-Ⅱproteins ( P<0.05 ) .After inhibition of autophagy by WTM in DDP-treated cells, cell viability was obviously decreased and apoptosis was increased (P<0.05);DDP combined with WTM observably enhanced cleavage of poly ADP-ribose polymerase 1 ( PARP-1 ) and cleaved-caspase-3 which is apop-tosis related proteins ( P<0.05 ) .Conclusions Autophagy can protect T24 cells against ciplatin-induced apop-tosis, the possible mechanism of autophagy is the ERK signaling pathway is activated .关键词
膀胱癌/顺铂/自噬/p-ERKKey words
bladder cancer/cisplatin/autophagy/p-ERK分类
医药卫生引用本文复制引用
刘言,谷文,印胡滨,苟欣,何卫阳..顺铂对膀胱癌细胞自噬和凋亡的作用及其相关性[J].基础医学与临床,2017,37(2):176-182,7.基金项目
国家自然科学基金(81370706,81372758);重庆市卫生和计划生育委员会重点资助项目 ()