丙戊酸钠诱导kasumi-1细胞分化与凋亡机制的探讨  

Induction of differentiation and apoptosis of sodium valproate on kasumi-1 cells

作　　者：赵淑清[1] 杨晨敏[1] 陈丽[2] 李军民[2] 

机构地区：[1]上海交通大学医学院附属瑞金医院卢湾分院血液科,上海200020 [2]上海交通大学医学院附属瑞金医院血液科上海血液学研究所,上海200025

出　　处：《中华肿瘤防治杂志》2010年第15期1180-1184,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：上海市卫生局青年科研基金项目(2007Y67)

摘　　要：目的:探讨组蛋白去乙酰化酶抑制剂丙戊酸钠(sodium valproate,VPA)体外诱导白血病细胞kasumi-1的分化和凋亡作用。方法:MTT实验和台盼蓝拒染法检测VPA对细胞的增殖抑制,流式细胞仪检测细胞分化和凋亡及进行细胞周期分析,蛋白质印迹方法检测组蛋白H3(lys9)的乙酰化水平变化及p21Waf1/Cip1蛋白的表达。结果:VPA可以抑制kasumi-1细胞增殖。VPA作用后,细胞周期阻滞在G0/G1期,该期细胞由(53.07±6.05)%增加到(78.97±5.82)%,P<0.05。在较低浓度(0.5mmol/L),VPA可以诱导kasumi-1细胞髓系分化,其表面抗原CD13表达从(20.47±0.21)%上升到(68.67±1.15)%,P=0.000。联合G-CSF后作用更为显著〔(87.80±1.21)%〕,P=0.000。在较高浓度(2mmol/L)下,VPA则诱导kasu-mi-1细胞凋亡,流式检测AnnexinⅤ结合力上升。VPA能够上调kasumi-1细胞组蛋白H3乙酰化水平,增加p21Waf1/Cip1蛋白的表达。结论:VPA能通过抑制HDAC活性,抑制细胞增殖,诱导kasumi-1细胞分化和凋亡。OBJECTIVE：To study the efficacy of sodium valproate （VPA）,a histone deacetylase inhibitor （HDACi） in induction of differentiation and apoptosis of kasumi-1 leukemic cell line.METHODS：Cell proliferation assays were performed using trypan blue staining and MTT methods.Cell cycle,differentiation and apoptosis were analyzed by flow cytometry.The protein level of acetylated histone H3 at lysine 9（H3-Ac-lys9）and p21Waf1/Cip1 were detected by Western blot.RESULTS：VPA inhibited the cell proliferation of kasumi-1 cells.After treatment with VPA,cell cycle was obviously arrested at G0/G1 phase,The percentage of cells in G0/G1 phase increased from （53.07±6.05）% to （78.97±5.82）%,P0.05.At low concentration （0.5 mmol/L）,VPA can induce myeloid differentiation in Kausmi-1 cells demonstrated by up-regulation of CD13 from（20.47±0.21）%to （68.67±1.15）%,P=0.000.When combined with granulocyte colony-stimulating factor （G-CSF）,the differentiation was remarkably enhanced to （87.80±1.21）%,P=0.000.At higher concentration （2 mmol/L）,VPA induce apoptosis of kasumi-1 cells by increased Annexin Ⅴ binding in flow cytometry.VPA significantly up-regulate the acetylation of H3-Ac-lys9 and p21Waf1/Cip1 in Kaumi-1 cells.CONCLUSION：VPA can inhibit the proliferation and induce differentiation and apoptosis in kasumi-1 cells through HDAC inhibiting.

关 键 词：组蛋白脱乙酰基酶类 丙戊酸 白血病 细胞分化 

分 类 号：R733.7[医药卫生—肿瘤]