硼替佐米或联合三氧化二砷诱导HL-60细胞凋亡实验研究

HL-60 cell apoptosis induced by bortezomib alone or in combination with arsenic trioxide in vitro

目的探讨硼替佐米单独或联合三氧化二砷对HL-60细胞凋亡的影响。方法不同浓度硼替佐米、三氧化二砷处理细胞12～48h,采用MTT比色法检测细胞增殖活性;DNA凝胶电泳、细胞形态学观察、流式细胞仪检测细胞凋亡。结果10～50nmol/L硼替佐米可有效抑制HL-60细胞增殖,并诱导其发生凋亡。其中10nmol/L剂量处理12h,即有细胞凋亡发生,延长作用时间或增加药物剂量,细胞凋亡率明显增加。选择15μmol/L三氧化二砷与10nmol/L硼替佐米联合应用,可见HL-60细胞凋亡率比两种药物单独使用时显著增加。结论硼替佐米对HL-60细胞存在时间和剂量依赖性的细胞凋亡效应,与三氧化二砷联合具有明显的协同作用。

Objective To investigate the effect ofbortezomib alone and in combination with arsenic trioxide on apoptosis of HL-60 cells. Methods HL-60 cells were treated with bortezomib alone or in combination with arsenic trioxide for 12 to 48 h and the cell proliferation was analyzed with MTT assay, and cell apoptosis detected by DNA gel electrophoresis, fluorescence microscopy and flow cytometry. Results At the concentrations of 10 to 50 nmol/L, bortezomib effectively inhibited HL-60 cell proliferation, and induced cell apoptosis. A 12-hour bortezomib treatment at 10 nmol/L was sufficient to induce cell apoptosis, and prolonged treatment or increased concentration significantly increased HL-60 cell apoptotic rate, Combined treatment of the cells with bortezomib （10 nmol/L） and arsenic trioxide （15 μmol/L） resulted in an even higher cell apoptosis rate than that induced by the respective agent alone. Conclusion Bortezomib can induce HL-60 cell apoptosis in a time- and dose-dependent manner, and a synergistic effect can be observed of bortezomib and arsenic trioxide in apoptosis induction.