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.
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)
