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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 study the mechanism of action of novel PI3K / mTOR double inhibitor NVP-BEZ235 on diffuse large B cell line in vitro. Methods: The effects of NVP-BEZ235 on the proliferation of SUDHL-4 and DB cells in diffuse large B cell line were detected by CCK-8 assay. Cell cycle and apoptosis were detected by flow cytometry. The protein and PI3K / AKT / Changes of molecules, cell cycle and apoptosis related molecules in mTOR signaling pathway. Results: NVP-BEZ235 could inhibit the proliferation of SUDHL-4 and DB in diffuse large B cell line in a dose-dependent manner; arrest cell cycle in G0 / G1 phase and promote cell apoptosis; Western blotting showed that NVP-BEZ235 could Inhibit the activity of key molecules in PI3K / AKT / mTOR signaling pathway, down-regulate cell cycle related proteins and up-regulate apoptosis-related proteins. Conclusion: PI3K / mTOR dual inhibitor NVP-BEZ235 can inhibit the growth of diffuse large B cell line SUDHL-4 and DB in vitro and block the cell cycle in G0 / G1 phase and promote cell apoptosis.