Depsipeptide联合阿糖胞苷、多柔比星对人白血病细胞株的抑制效应

Growth inhibition of depsipeptide combined with cytorabine or doxorubicin on human leukemia cells

  • 摘要: 目的:研究组蛋白去乙酰化酶抑制剂Depsipeptide联合阿糖胞苷(Ara-c)、多柔比星(DNR)对人白血病细胞株K562、HL-60的抑制效应,并定量分析其协同、相加或拮抗作用。方法:以不同浓度的Depsipeptide、Ara-c、DNR单独或联合处理K562、HL-60细胞株48 h,MTT法测定细胞生长抑制作用,中效原理法判断联合用药的相互作用。结果:①三种药物单用或两药联合作用于两种细胞株,均呈现剂量依赖性抑制效应。②Depsipeptide与Ara-c或DNR联合作用于K562、HL-60细胞株,在低抑制效应时呈现拮抗作用,高抑制效应时呈现协同作用。③改变两药的联合比率影响合用效应。结论:Depsipeptide作为一类新型的抗肿瘤药物,可有效抑制人白血病细胞株K562、HL-60增殖;其与传统化疗药物Ara-c、DNR联合可呈现协同作用;联合用药比率是影响抑制效应的重要因素。

     

    Abstract: Objective:To investigate growth inhibition of depsipeptide combined with cytorabine or doxorubicin on human leukemia K562 and HL-60 cells,and analyze synergistic or antagonistic effect of combined agents.Methods:The MTT assay was used to test growth inhibition after 48h of exposure to depsipeptide,cytorabine,doxorubicin alone or two agents.The drugs interaction were analyzed by using the median-effect method of Chou and Talalay.Results:①The growth inhibition of K562 or HL-60 was dose-dependent after exposure to depsipeptide,cytorabine,doxorubicin alone or two agents.②The interaction of depsipeptide with cytorabine or doxorubicin were antagonistic at lower concentration,and synergistic at higher concentration.③ The ratio of drug concentration could influence the combination index(CI).Conclusion:As a new antitumor agent,the histone deacetylase inhibitor depsipeptide could inhibit the proliferation of human leukemia K562 and HL-60 cells effectively.Depsipeptide combined with the chemotherapeutic drugs cytorabine or doxorubicin could display synergistic activity.The ratio of drug concentration is a significant factor that influence on the growth inhibition.

     

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