伏立诺他与左旋苯丙氨酸氮芥对人类多发性骨髓瘤细胞的协同作用  

Synergistic effect of vorinostat and melphalan on human multiple myeloma cell lines

作　　者：熊文杰[1] 凌燕[1] 冯春锐[1] 陶小梅 张琼丽[1] 杜新[1] 

机构地区：[1]深圳市第二人民医院血液科,深圳518035 [2]深圳市血液病研究所(

出　　处：《肿瘤研究与临床》2012年第6期386-388,共3页Cancer Research and Clinic

基　　金：2010年深圳市科技计划（医疗卫生类）（201003039）

摘　　要：目的观察体外伏立诺他和左旋苯丙氨酸氮芥联合对人类多发性骨髓瘤细胞株U266、KM3的抗瘤作用。方法应用MTT法分别测定伏立诺他和左旋苯丙氨酸氮芥不同浓度对骨髓瘤细胞株U266、KM3的抗瘤作用，计算两药的IC50值；应用MTT法测定固定一种药物浓度联合不同浓度另一药物时对U266、KM3的抑制作用，计算药物联合指数（CI），判断药物相互作用。结果伏立诺他单药对U266细胞的IC50值介于5．0～7．5μmol／L，对KM3细胞的‰值介于2．5～5．0μmol／L；左旋苯丙氨酸氮芥单药杀伤U266细胞的IC50值介于40—60μmol／L，杀伤KM3细胞的IC50值介于60。80μmol／L。固定伏立诺他浓度（U266细胞中为1．25μmol／L，KM3细胞中浓度为1．0μmol／L），在U266细胞中左旋苯丙氨酸氮芥浓度为20、40、60、80μmol／L时均CI〈0．9，表现为协同作用，在KM3细胞中左旋苯丙氨酸氮芥浓度为40、60、80、100μmol／L时均CI〈0．9，表现为协同作用；固定左旋苯丙氨酸氮芥浓度（U266细胞中为10μmol／L，KM3细胞中浓度为20μmol／L），在U266细胞中伏立诺他浓度为2．5、5．0、7．5μmol／L时均CI〈0．9，表现为协同作用，在KM3细胞中伏立诺他浓度为1．0、2．5、5．0μmol／L时均CI〈0．9，表现为协同作用；当伏立诺他浓度为7．5μmol／L联合左旋苯丙氨酸氮芥20μmol／L时呈现相加作用（CI=0．93）。结论体外伏立诺他单药对两种多发性骨髓瘤细胞株有明显的杀伤作用，与左旋苯丙氨酸氮芥有协同抗骨髓瘤细胞作用。Objective To observe the anti-tumor effect on human multiple myeloma cell lines U266 and KM3 with a combination of varinostat and melphalan in vitro. Methods The eell proliferation of U266 and KM3 was datected with MTT assay when treated them with vorinostat alone and melphalan alone,then calculate their ICso values respectively. Fixed the concentrations of vorinostator melphalan, the cell proliferation was datected in combination with melphalan/vorinostat in seriesly concentrations by MTT assay. Then to calculate drug combination index（CI）. Results The IC50 value of U266 was 5.0-7.5 μmol/L and that of KM3 was 2.5-5.0 μmol/L when treated by vorinostat alone, the IC50 value of U266 was 40-60 μmol/L and that of KM3 was 60-80 Ixmol/L treated by melphalan alone. When fixed the concentration of vorinostat（in U266 the concentration was 1.25 I.Lmol/L, in KM3 the concentration was 1.0 μmol/L）, Synergism （CI〈0.9） was observed when the concentrations of melphalan were 20μmol/L,40 μmol/L,60 μmol/L and 80 μmol/L in U266,40 μmol/L, 60 μmol/L, 80 μmol/L and 100 Ixmol/L in KM3; When fixed the eoncertration of melphalan （in U266, was 10 μmol/L, in KM3 was 20 μmol/L）, synergism （CI〈0.9） was observed when the concentrations of vorinostat were 1.0 μmol/L,2.5 μmol/L,5.0 μmol/L and 7.5 μmol/L in U266,and 1.0 μmol/L,2.5μmol/L, 5.0 μmol/L in KM3. An additive effect was observed with the czombination of vorinostat 7.5 μmol/L plus melphalan 20 μmol/L in KM3 （CI=0.93）. Conclusion Vorinostat had potential anti-myeloma effect alone, and had synergistic anti-tumor effect with melphalan in vitro.

关 键 词：多发性骨髓瘤 伏立诺他 左旋苯丙氨酸氮芥 U266细胞 KM3细胞 

分 类 号：R733.3[医药卫生—肿瘤]