Quercetin inhibits leukemia cells by regulating PI3k/Akt pathway in vitro / 白血病·淋巴瘤

ABSTRACT

Objective To study the anti-tumor activity of quercetin in NB4 leukemia cells and the roles of PI3K/Akt,bcl-2,and Bax on the quercetin-induced apoptosis,and to investigate the potential underlying mechanism.Methods MTT assay was used to monitor cell proliferation,Hoechst 33258 fluorescent staining and flow cytometry were employed to detect apoptosis in NB4 cells.Western blot was used to detect the expression changes of related proteins in quercetin treated NB4 cells.Confocal laser microscopy was used to test the distributional variation of Akt between cytoplasm and nucleus.Results Quercetin significantly inhibited the NB4 cell proliferation in a dose-and time-dependent manner (20-160 μ mol/L).In addition,treated by 20,40 80 μmol/L quercetin,the rates of apoptosis were (9.25±0.11) ％,(20.83±2.10) ％and (41.43±2.90) ％,there were statistical difference compared with blank cells (t were 4.14,6.56 and 7.02,all P ＜ 0.05).This was concentration dependent and accompanied by morphological changes characteristic of apoptosis.Further,quercetin induced a G~M arrest,which might account for its cytotoxic effects.Quercetin decreased PI3k/Akt expression and caused an inhibition of the anti-apoptotic protein bcl-2,while increasing the expression of Bax.Quercetin had no effects on total Akt,but it promoted Akt translocation from cell nucleus to the cytoplasm (F =15.12,P ＜ 0.05).Conclusion Quercetin induces the leukemia NB4 cell apoptosis by affecting multiple signal pathways and plays a strong anti-leukemia effect.In addition,our results suggest that PI3K/Akt pathway could be a novel target for the leukemia chemotherapy.