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

作　　者：刘毅[1] 杨平地[1] 于晓妉[2] 

机构地区：[1]第二军医大学临床医学院海军总医院血液科,北京100037 [2]军事医学科学院基础医学研究所,北京100850

出　　处：《军医进修学院学报》2007年第4期271-273,共3页Academic Journal of Pla Postgraduate Medical School

基　　金：国家自然科学基金资助重点项目(30330620)

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。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, eytorabine, doxorubiein 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, eytorabine, doxorubiein alone or two agents. ②The interaction of depsipeptide with eytorabine or doxorubiein 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 deaeetylase inhibitor depsipeptide could inhibit the proliferation of human leukemia K562 and HL-60 cells effectively. Depsipeptide combined with the chemotherapeutic drugs eytorabine or doxorubiein could display synergistic activity. The ratio of drug concentration is a significant factor that influence on the growth inhibition.

关 键 词：DEPSIPEPTIDE 阿糖胞苷 多柔比星 K562细胞 HL-60细胞 

分 类 号：R557[医药卫生—血液循环系统疾病]