mTOR通路抑制剂GDC-0349对CCRF-CEM细胞增殖和凋亡的影响

目的:探讨mTOR通路抑制剂GDC-0349对急性T淋巴细胞白血病细胞株CCRF-CEM细胞增殖和凋亡的影响。方法:不同浓度GDC-0349作用于CCRF-CEM细胞，采用CCK-8法检测细胞增殖；流式细胞术检测细胞凋亡率；Western blot 检测凋亡相关蛋白及AKT/mTOR通路相关蛋白的表达。结果:GDC-0349作用于CCRF-CEM细胞后细胞增殖率减少且凋亡率增加（P＜0.05)；凋亡相关蛋白Caspase3和BCL2下调，Cleaved-Caspase3增加（P＜0.05)；通路相关蛋白AKT、p-AKT及p-mTOR下调（P＜0.05）。结论:GDC-0349能够抑制AKT/mTOR通路活化，从而促进CCRF-CEM细胞凋亡，抑制细胞增殖。

Effect of GDC-0349,the mTOR pathway inhibitor,on proliferation and apoptosis of CCRF-CEM cells

Objective:To investigate the effect of GDC-0349,the mTOR pathway inhibitor,on proliferation and apoptosis of acute T lymphocytic leukemia cell line CCRF-CEM.Methods:Different concentrations of GDC-0349 were applied to CCRF-CEM cells.Cell proliferation was detected by CCK-8 method.Apoptosis rate was detected by flow cytometry.Expressions of apoptosis-related proteins and AKT/mTOR pathway proteins were detected by Western blot.Results:In CCRF-CEM cells with GDC-0349,the cell proliferation rate decreased and the apoptotic rate increased (P＜0.05).Caspase3 and BCL2 were down-regulated (P＜0.05) and Cleaved-Caspase3 was up-regulated (P＜0.05).The expressions of AKT/mTOR pathway-related proteins were down-regulated,such as AKT,p-AKT and p-mTOR (P＜0.05).Conclusion:GDC-0349 can inhibit the AKT/mTOR pathway,then promote cell apoptosis and inhibit cell proliferation in CCRF-CEM cells.