三氧化二砷对多发性骨髓瘤细胞的影响

Effects of arsenic trioxide on multiple myeloma cells

目的 :了解多发性骨髓瘤细胞对As2 O3 的反应及其可能机制。方法 :使用多发性骨髓瘤细胞系RPMI82 2 6和U2 6 6细胞作为体外模型。细胞凋亡经细胞形态学、流式细胞仪和DNA凝胶电泳判定。通过测定细胞内荧光染料Rhodamine 12 3的染色强度分析线粒体跨膜电位 (ΔΨm) ,并采用蛋白印迹分析蛋白剪切情况。结果 :不同浓度的As2 O3 对RPMI82 2 6和U2 2 6细胞产生不同的效应 :0 1～ 0 5 μmol/L的As2 O3 抑制其增殖 ,2 0 μmol/L的As2 O3 诱导其凋亡 ,而 1 0 μmol/L的As2 O3 在抑制细胞增殖的同时轻度诱导细胞凋亡。As2 O3 诱导的MM细胞凋亡伴随线粒体ΔΨm下降和caspase 3的活化。结论 :As2 O3 具有一个相对较广的诱导凋亡效应谱 ,而线粒体ΔΨm破坏是As2 O3

Purpose:To investigate the response of multiple myeloma cells to arsenic trioxide (As 2O 3) and their possible mechanisms.Methods:Multiple myeloma derived cell lines RPMI 8226 and U266 cells were used as in vitro models. Apoptosis was assessed by morphology, flow cytometry, and DNA electrophoresis. Mitochondrial transmembrane potentials (ΔΨm) were detected by measuring cellular Rhodamine 123 staining intensity on flow cytometry. Caspase 3 activation was assessed by means of western blot.Results:Different concentrations of As 2O 3 exerted the dissimilar effects on RPMI8226 and U266 cell lines in the time dependent manner. 0.1 to 0.5 μmol/L As 2O 3 inhibited cell proliferation without apoptosis induction, 2.0 μmol/L As 2O 3 induced cell apoptosis, while 1.0 μmol/L As 2O 3 inhibited proliferation with weak apoptosis inducing effect. Futhermore,As 2O 3 induced apoptosis was parallel to the ΔΨm collapse and caspase 3 activation in the presence of intact membrane.Conclusions:As 2O 3 has a wide effect spectrum in term of apoptosis induction, and the ΔΨm collapse ia a pivotal and common mechanism for As 2O 3 induced apoptosis.