【摘要】 目的 研究氟达拉滨(Fludarabine,FDB)联合丙戊酸(valproic acid,VPA)对慢性粒细胞白血病(chronicmyeloid leukemia,CML)细胞株K562增殖及凋亡的影响,并探讨其可能的作用机制。方法 慢性粒细胞白血病细胞株K562,单独使用不同浓度的FDB(1,5,10μmol/L)或VPA(1,2.5,5 mmol/L),或联合使用FDB和VPA处理K562细胞,采用MTT法检测细胞增殖情况,并观察其有效的作用浓度;流式细胞仪检测K562细胞周期变化;western blot检测凋亡相关蛋白及组织蛋白酶B的表达变化。结果 单独使用FDB或VPA均可明显抑制K562细胞的增殖,呈剂量依赖性,并使K562细胞停滞在G0/G1期,联合使用VPA能增强FDB对K562细胞的凋亡诱导作用。同时检测到FDB和VPA能诱导溶酶体中组织蛋白酶B的表达。结论 联合使用FDB和VPA可诱导K562细胞溶酶体中组织蛋白酶B的表达及活性,从而启动溶酶体介导的细胞凋亡过程,明显抑制K562细胞的增殖,并促进K562细胞的凋亡,提高治疗效果,为临床抗肿瘤治疗提供新的指导方向。更多还原

【Abstract】 Objective To investigate the proliferation-inhibitory and apoptotic-induction effect of fludarabine(FDB) and valproic acid(VPA) in human chronic myeloid leukemia(CML) cells-K562 cells.Methods The cell proliferation inhibitory rates of K562 cells treated with different concentration of FDB(1,5,10 μmol/L) or VPA(1,2.5,5 mmol/L) alone and in combination were detected by MTT assay.The change of cell cycle of K562 cells was detected by flow cytometer.The expression level of apoptosis maker-caspase-3 and cathepsin B was measured by western blot.Results Different concentration of FDB or VPA alone or in combination could obviously inhibit the proliferation of K562 cells in a dose-dependent manner(P<0.05),FDB and VPA could block K562 cells in G0/G1 phase and activate the cell apoptosis through lysosome-cathepsin B pathway.Conclusions FDB and VPA had anti-tumor effect on K562 cells in vitro through inhibiting cell proliferation and inducing cell apoptosis,which might be related to the regulation of lysosome-cathepsin B pathway.FDB and VPA may be used as new anti-tumor agents for the treatment of CML.更多还原