阿糖胞苷诱导白血病细胞株U937自噬作用的实验观察  

Autophagy of acute myelogenous leukemia cell line U937 under induction by cytarabine

作　　者：陈丽韵[1] 贾培敏[2] 童建华[2] 李军民[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院血液科,上海200025 [2]上海交通大学医学院附属瑞金医院上海血液学研究所,上海200025

出　　处：《诊断学理论与实践》2013年第2期185-188,共4页Journal of Diagnostics Concepts & Practice

基　　金：国家自然科学基金(81270621)

摘　　要：目的:观察阿糖胞苷(Ara-C)诱导白血病细胞株U937自噬作用,并探讨其可能的机制。方法:采用细胞计数仪计数,测得不同浓度Ara-C处理U937细胞后24 h和48 h的生长抑制率;用透射电镜观察细胞的超微结构变化,并应用蛋白印迹法检测自噬相关蛋白LC3、p62及PI3K-Akt-mTOR通路的蛋白水平。结果:细胞计数发现,不同浓度Ara-C作用的各组细胞生长均受到明显抑制。Ara-C处理细胞24 h后,在透射电镜下观察,可见细胞质中出现大量双层膜包裹形成的自噬体,内含细胞器或细胞质;蛋白印迹法检测结果显示,LC3-Ⅱ表达水平明显增高;同时Akt-mTOR通路受到明显抑制。结论:Ara-C能够抑制白血病细胞株U937细胞增殖,其通过抑制Akt-mTOR信号通路诱导细胞发生自噬,为Ara-C抗肿瘤机制提供了新思路。Objective To investigate the mechanism of cytarabine-induced autophagy in acute myelogenous leukemia cell line U937. Methods Cell proliferation inhibition rate was calculated by cell count analyzer after 24 and 48 hours treatment with cytarabine in different concentrations. Uhrastructural cellular changes were observed under transmission electron microscope （TEM）. Levels of LC3, p62 and PI3K-Akt-mTOR were detected by Western blot. Results After treated with cytarabine, the proliferation of U937 was inhibited in a concentration and time-dependent manner. TEM examination revealed the appearance of large number of autophagosome with double membrane structure in cytoplasm. Simultaneously, elevated level of LC3-Ⅱ was detected. Meanwhile the inhibition of signaling pathway of Akt-mTOR was also detected. Conclusions The growth of U937 cells is inhibited and autophagy is induced by cytarabine with accompanying inhibited Akt-mTOR signaling pathway.

关 键 词：阿糖胞苷 自噬 急性髓系白血病 机制 

分 类 号：R733.7[医药卫生—肿瘤]