三氧化二砷联合姜黄素对KG1a细胞的协同杀伤作用  

Synergistic Killing Effect of Arsenic Trioxide Combined with Curcumin on KG1a Cells

作　　者：范佳鑫[1,2] 曾英坚[1,2] 吴建伟[1,2] 李章球[1,2] 李元明[1,2] 郑荣[1,2] 翁光样[3] 郭坤元[3] 

机构地区：[1]暨南大学附属江门中医院 [2]江门市五邑中医院血液科,广东江门529000 [3]南方医科大学珠江医院血液科,广东广州510282

出　　处：《中国实验血液学杂志》2014年第5期1267-1272,共6页Journal of Experimental Hematology

基　　金：2013年广东省中医药管理局科研立项项目(20132046);2013年广东省江门市科技局科技计划立项项目(20130014)

摘　　要：本研究旨在探讨三氧化二砷联合姜黄素对KG1a细胞的增殖与凋亡的影响及可能的机制。采用MTT法检测细胞存活率;甲基纤维素集落形成实验检测细胞成集落能力;流式细胞术检测细胞表面分子、细胞凋亡率及细胞周期变化;瑞氏姬姆沙染色法观察细胞形态;Westerrn blot检测细胞BCL-2、BAX、PARP蛋白表达。结果表明:KG1a细胞表型为CD34+CD38-,HL-60细胞表型为CD34+CD38+;前者成集落能力比后者强。姜黄素及三氧化二砷单用对KG1a细胞增值抑制作用均具有剂量依赖性。联合用药与单药对比,前者细胞存活率、克隆形成集落数更低,而细胞凋亡率更高。联合用药能够降低细胞的BCL-2、PARP两种蛋白表达、增加BAX蛋白表达。结论:KG1a细胞是比HL-60细胞更早期的白血病干/祖细胞。三氧化二砷联合姜黄素能更有效抑制KG1a细胞增殖及诱导其凋亡,其机制可能与BCL-2、PARP蛋白表达下调、BAX蛋白表达上调有关。This study was aimed to explore the effect of arsenic trioxide combined with curcumin on proliferation and apoptosis of KG1a cells and its potential mechanism.The cell survival rate was mesured by MTT; colony formation capacity was examined by methylcellulose colony formation test; flow cytometry was used to analyse the cell surface molecules,cell apoptosis rate and cell cycle; the cell morphology was observed with Wright-Giemsa staining and the protein expression of BCL-2,BAX,PARP was detected by Western blot.The results showed that the phenotype of KGla cells was CD34 ＋ CD38-,while the phenotype of HL-60 cell was CD34 ＋ CD38 ＋.The former possessed a stronger colony ability than the latter.Effect of curcumin and arsenic trioxide alone on cell proliferation and inhibition was in dose-dependent manner.Compared with single drug-treatment group,the cell survival rate and colony number were lower,and the apoptosis rate was higher in combined drug-treatment group.Protein expression of BCL-2 and PARP was upregulated,while the protein expression of PARP was downregulated in the combined treatment group.It is concluded that compared with HL-60 cells,KG1a cells are the earlier leukemia stem/progenitor cells.Arsenic trioxide combined with curcumin can effectively inhibit the KG1 a cell proliferation and induce apoptosis,which may be associated with the downregulation of BCL-2 and PARP protein expression and the upregulation of BAX protein expression.

关 键 词：姜黄素 三氧化二砷 KG1a 细胞凋亡 

分 类 号：R733.71[医药卫生—肿瘤]