六亚甲基二乙酰胺对急性白血病细胞株HL-60和U937分化、凋亡的影响及其机制

被引:5
作者
王钦红
谢毅
范华骅
高跞
刘燕
谢彦晖
机构
[1] 复旦大学附属华山医院血液科,复旦大学附属华山医院血液科,上海血液中心血液工程研究室,上海血液中心血液工程研究室,上海血液中心血液工程研究室,复旦大学附属华山医院血液科上海,上海,上海
关键词
六亚甲基二乙酰胺; 细胞分化; 细胞凋亡; 细胞周期; 基因;
D O I
暂无
中图分类号
R733.7 [白血病];
学科分类号
100214 ;
摘要
目的 研究六亚甲基二乙酰胺 (HMBA)体外诱导HL 6 0和U937细胞分化、凋亡的作用及其机制。方法 流式细胞仪检测细胞分化抗原CD1 1b、CD1 4,细胞凋亡标记Annexin Ⅴ以及进行细胞周期分布和细胞内cyclinD、cyclinE、p2 7抗原的分析 ,RT PCR检测c myc、Rb、Bcl 2基因mRNA的表达。结果 HL 6 0、U937细胞经HMBA处理 72h后CD1 1b表达显著增高 ,高剂量HMBA促使Annexin Ⅴ表达增加。HMBA阻滞HL 6 0、U937细胞于G0 G1 期 ,并使该两种细胞内cyclinE表达显著下降 ,cyclinD、p2 7表达显著增高 ,呈剂量依赖关系 ;HMBA可使HL 6 0、U937细胞c myc、Bcl 2mRNA表达下调 ,而RbmRNA在HL 6 0细胞表达上调 ,在U937细胞则无显著改变。结论 HMBA能诱导HL 6 0、U937细胞出现明显的分化 ,高剂量的HMBA有促使HL 6 0、U937细胞凋亡的倾向 ,其机制可能是通过影响细胞周期调控分子以及有关的增殖分化相关基因的表达 ,从而抑制细胞增殖 ,促进细胞分化。
引用
收藏
页码:29 / 32
页数:4
相关论文
共 10 条
[1]  
Inducing differentiation of transformed cells with hybrid polar compounds: a cell cycle-dependent process. Marks PA,Richon VM,Kiyokawa H,et al. Proceedings of the National Academy of Sciences of the United States of America . 1994
[2]  
Regulation and function of Bcl-2 during differentiation-induced cell death in HL-60 promyelocytic cells. Benito A,Grillot D,Nunez G,et al. American Journal of Pathology . 1995
[3]  
Cell cycle exit during terminal erythroid differentiation is associated with accumulation of p27(Kipl) and inactivation cdk2 kinase. Hsieh FF,Barnett LA,Green WF,et al. Blood . 2000
[4]  
Retinoic acid-induced cell cycle arrest of human myeloid cell lines is associated with sequential downregulation of c-Myc and cyclin E and posttranscriptional up-regulation of p27(Kipl). Dimberg A,Bahram F,Karlberg I,et al. Blood . 2000
[5]  
Manipulating the onset of cell cycle withdrawal in differentiated erythroid cells with cyclin-dependent kinases and inhibitors. Matushansky I,Radparvar F,Skoultchi AI. Blood . 2000
[6]  
Modulation of retinoblastoma gene in normal adult hematopoiesis: peak expression and functional role in advanced erythroid differentiation. Condorelli GL,Testa U,Valtieri N,et al. Proceedings of the National Academy of Sciences of the United States of America . 1995
[7]  
1, 25-Dihydroxy-vitaminD3 induces differentiation of a retinoic acid-resistant acute promyelocytic leukemia cell line(UF-1) associated with expression of p21 and p27. Muto A,Kizaki M,Yamato K,et al. Blood . 1999
[8]  
Comparisonness of the effectiveness of adenovirus vectors expressing cyclin kinase inhibitor p16INK4A, p18INK4C, p19INK4D, p21 (WAF1 CIP1) and p27KIP1 in inducing cell cycle arrest, apoptosis and inhibition of tumorigenicity. Schreiber M,Muller WJ,Singh G,et al. Oncegene . 1999
[9]  
Leukemia[P]. 英国专利:GB0221802D0,2002-10-30
[10]  
Rapamycin-induced G1 arrest in cycling B-CLL cells is associated with reduced expression cyclin D3, cyclin E, cyclin A, and survivin. Decker T,Hipp S,Ringshausen I,et al. Blood . 2003