硼替佐米单用或联合三尖杉酯碱体外诱导HL60细胞凋亡实验研究_医学论文.docVIP

硼替佐米单用或联合三尖杉酯碱体外诱导HL60细胞凋亡实验研究_医学论文 硼替佐米单用或联合三尖杉酯碱体外诱导HL60细胞凋亡实验研究_医学论文 作者：孙启鑫，孟凡义，扶云碧，李利【摘要】 　　 本研究探讨硼替佐米（bortezomib， Bor）单用或联合三尖杉酯碱（harringtonine， HT）对HL60细胞凋亡的影响。以不同浓度Bor、HT处理HL60细胞12-48小时，采用MTT比色法检测细胞增殖活性，以DNA凝胶电泳、荧光显微镜检、流式细胞术检测细胞凋亡。结果表明： 10-50 nmol/L Bor可有效抑制HL60细胞增殖，并诱导其凋亡。其中10 nmol/L剂量处理12小时即有细胞凋亡发生，延长作用时间或增加药物剂量可使细胞凋亡率明显增加。30 nmol/L HT与10 nmol/L Bor联合应用时，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： Bor对HL60细胞具有时间和剂量依赖性的细胞凋亡诱导效应，与HT联合应用有明显的协同作用。 【关键词】 硼替佐米； 三尖杉酯碱； 凋亡 　　 Induction of Apoptosis in HL60 Cells by Bortezomib alone or in Combination with Harringtonine In Vitro Abstract The aim of this study was to investigate the effect of bortezomib alone and in combination with harringtonine on apoptosis of HL60 cells. HL60 cells were treated with bortezomib, harringtonine in different concentrations for 12-48 hours. Cell proliferation was analyzed by MTT assay； the apoptosis of HL60 cells was observed by DNA gel electrophoresis， fluorescence microscopy and flow cytometry. The results showed that 10-50 nmol/L bortezomib could effectively inhibit HL60 cell proliferation, and induced its apoptosis. After treating for 12 hours, 10 nmol/L bortezomib could trigger cells apoptosis. With time prolongation or dose increase, HL60 cell apoptotic rate significantly increased. Furthermore, coadministration of bortezomib (10 nmol/L) with harringtonine (30 nmol/L) resulted in a higher cell apoptotic rate when compared with that induced by those agents used alone. It is concluded that the bortezomib can induce HL60 cells apoptosis in a timeanddosedependent manner and synergistic effectiveness can be found when bortezomib combined with harringtonine. Key words bortezomib harringtonine apoptosis J Exp Hematol 2007 15(2):233-236 急性白血病是一类恶性克隆性疾病，虽然其治疗水平近年来已有了明显提高，但仍有相当一部分患者因疾病复发或耐药而转变成难治的白血病，因此积极寻求新的治疗方法在当前仍然显得尤为重要。硼替佐米（bortezomib，Bor）是一种新型抗肿瘤靶向治疗药物，目前主要用于复发或难治的多发性骨髓瘤的治疗，并已显示出良好的疗效［1］。研究显示Bor在体外对多种恶性肿瘤细胞均具有良好的疗效，但在急性白血病方面的研究至今报道很少，更未见与三尖杉酯碱（harringtonine, HT)联合应用的研究报告。本研究首次