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  

Effect of HMBA on differentiation and apoptosis of HL-60 and U937 cells and its mechanism

作　　者：王钦红[1] 谢毅[1] 范华骅[2] 高跞[2] 刘燕[2] 谢彦晖[1] 

机构地区：[1]复旦大学附属华山医院血液科,上海200040 [2]上海血液中心血液工程研究室

出　　处：《中华血液学杂志》2004年第3期154-157,共4页Chinese Journal of Hematology

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。Objectives To explore the effect of hexamethylene bisacetamide(HMBA) on the differentiation and apoptosis of HL-60 and U937 cells,and its mechanism. Methods Flow cytometry was used to evaluate the expressions of cellular surface antigen CD_ 11b ,CD_ 14 ,apoptotic marker Annexin Ⅴ,cell cycle distribution and endocytic antigen cyclin D,cyclin E and p27. Changes of c-myc,Rb,Bcl-2 gene mRNA levels were detected by RT-PCR. Results After 72 hours of HMBA treatment,CD_ 11b expressions increased significantly,apoptosis increased under high-dose HMBA,cells were arrested in G_0/G_1 phase and reduced cyclin E,increased cyclin D and p27 were significant in a dose-dependent manner in HL-60 and U937 cells. RT-PCR showed that c-myc and bcl-2 mRNA was significantly down-regulated and Rb mRNA up-regulated in HL-60 and U937 cells. Conclusion HMBA can induce the differentiation of HL-60 and U937 cells,while apoptosis of these cell is induced only by high dose of HMBA. The possible mechanism of HMBA inducing differentiation might be related to the changes of cell cycle regulators and certain proliferation and differentiation related genes.

关 键 词：六亚甲基二乙酰胺 急性白血病 HL-60细胞株 U937细胞株 细胞分化 细胞凋亡 流式细胞仪 

分 类 号：R733.7[医药卫生—肿瘤]