新型化合物FK106诱导白血病细胞凋亡的作用研究

Study on the effect of new compound FK106 on apoptosis induced by leukemia cells

目的研究新型化合物FK106对白血病细胞增殖的抑制作用及其可能的机制。方法采用噻唑蓝(MTT)法检测FK106对白血病MV4-11细胞存活率的影响,采用PI染色流式细胞仪检测FK106对细胞周期的影响,通过Annexin V-FITC/PI双染流式细胞仪检测FK106对细胞凋亡的影响,采用Western blot检测凋亡相关蛋白表达的影响。结果FK106对白血病细胞MV4-11的增殖具有抑制作用,且在0.1-1.0μmol·L^-1浓度范围内,对白血病MV4-11的抑制率具有浓度、时间依赖关系;FK106能阻滞MV4-11细胞G 0/G 1期;随着FK106浓度的增加,MV4-11细胞凋亡率呈现增高的趋势,并呈剂量依赖性;FK106可以抑制Bcl-2和Fas mRNA的表达,同时Bax和Caspase-3 mRNA表达明显增加,以上均呈依赖性。结论FK106能抑制人白血病细胞MV4-11细胞的增殖,并诱导其发生凋亡,可能通过Bcl-2和Fas途径诱导MV4-11细胞凋亡,具有较好的临床应用前景。

Objective To study the inhibitory effect of new compound FK106 on leukemia cell proliferation and its possible mechanism.Methods The effects of FK106 on the cell survival rate of leukemia MV4-11 were detected by MTT,the effects of FK106 on cell cycle were detected by PI staining flow cytometry,and the effects of FK106 on apoptosis were detected by Annexin V-FITC/PI double staining flow cytometry.the expression of apoptosis related proteins were detected by Western blot.Results FK106 had inhibitory effect on the proliferation of leukemia cell MV4-11,and the inhibition rate had concentration and time-dependent within the concentration of 0.1-1.0μmol·L^-1 of FK106.FK106 can block the MV4-11 cell G 0/G 1 phase.The apoptosis rate of MV4-11 cells had an increasing trend with the increase of FK106 concentration,and the apoptosis rate of cells was dose-dependent.FK106 inhibited the expression of Bcl-2 and Fas mRNA,while Bax and Caspase-3 mRNA expression increased significantly,and the expression of these protein were dose-dependent.Conclusion FK106 can inhibit the proliferation of MV4-11 cells of human leukemia cells and induce apoptosis.It may induce MV4-11 cells apoptosis through Bcl-2 and Fas pathways,which has a good clinical application prospect.