PI3K/mTOR双重抑制剂NVP-BEZ235对弥漫大B细胞株靶向作用的体外研究  

The in vitro study of targeting activity of a novel dual PI3K/mTOR inhibitor NVP-BEZ235 on diffuse large B-cell lymphoma cell line

作　　者：付婉彬[1] 王文方[1] 刘之茵[1] 陈丽韵[1] 郭沛[1] 李军民[1] 徐子真[1,2] 

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血液学研究所,上海200025 [2]上海交通大学医学院附属瑞金医院检验系,上海200025

出　　处：《诊断学理论与实践》2013年第4期414-418,共5页Journal of Diagnostics Concepts & Practice

基　　金：上海市科学技术委员会科研创新项目(11140901200)

摘　　要：目的:在体外水平研究新型PI3K/mTOR双重抑制剂NVP-BEZ235对弥漫大B细胞株的靶向作用机制。方法:采用CCK-8法检测NVP-BEZ235对弥漫大B细胞株SUDHL-4和DB细胞增殖的影响,流式细胞术检测细胞周期和细胞凋亡,蛋白印迹法检测靶蛋白及PI3K/AKT/mTOR信号转导通路上下游分子、细胞周期及凋亡相关分子的变化。结果:NVP-BEZ235可呈剂量依赖性地抑制弥漫大B细胞株SUDHL-4和DB的增殖;使细胞周期阻滞在G0/G1期,并促进细胞凋亡;蛋白印迹检测显示NVP-BEZ235能够抑制PI3K/AKT/mTOR信号通路中关键分子的活性,下调细胞周期相关蛋白,上调凋亡相关蛋白。结论:PI3K/mTOR双重抑制剂NVP-BEZ235可在体外水平抑制弥漫大B细胞株SUDHL-4和DB的生长,使细胞周期阻滞在G0/G1期,促进细胞凋亡。Objective： To investigate the targeting activity mechanism of a novel dual PI3K/mTOR inhibitor NVP- BEZ235 on diffuse large B-cell lymphoma cell lines in vitro. Methods： CCK-8 assay was used to assess the influence of NVP-BEZ235 on cell proliferation. Flow cytometry was performed to examine the cell cycle and apoptosis. The targeted proteins,changes of up-and down-stream molecules in PI3K/AKT/mTOR signaling pathway, cell cycle proteins and apoptosis-related proteins were detected by Western blot. Result： Cell proliferation was inhibited in a dose-dependent manner, cell cycle was arrested in Gc/Gj phase and cell apoptosis was induced. Western blot assay showed that NVP- BEZ235 could inhibit the activity of key molecule of PI3K/AKT/mTOR pathway, down-regulate cell cycle-related proteins, and up-regulate apoptosis associated proteins. Conclusions： The dual PI3K/mTOR inhibitor NVP-BEZ235 could inhibit the proliferation and induce the apoptosis of diffuse large B-cell lymphoma cell lines SUDHL-4 and DB in vitro.

关 键 词：P13K mTOR途径 NVP—BEZ235 弥漫大B细胞株 凋亡 细胞周期 

分 类 号：R587.1[医药卫生—内分泌]