全反式维甲酸联合丙戊酸钠诱导白血病细胞分化过程中BRD4表达变化及其作用的研究  

Study of all-trans retinoic acid combined with sodium valproate induced changes in the expression of BRD4 and its role in differentiation of leukemia cells

作　　者：韦若颍[1,2,3] 毕可红[1] 姜国胜[2,3] 宋冠华[2,3] 张之勇[2,3] 张文[2,3] 郭燕[1] 王岩[1,2,3] 邱效东[1] 潘素飞[2,3] 史露露[2,3] 

机构地区：[1]山东省千佛山医院血液科,山东济南250014 [2]山东省医学科学院基础医学研究所 [3]济南大学山东省医学科学院医学与生命科学学院,山东济南250062

出　　处：《中国医药科学》2013年第7期30-32,49,共4页China Medicine And Pharmacy

基　　金：国家科学自然基金资助项目(81172792)

摘　　要：目的探讨全反式维甲酸(ATRA)联合丙戊酸钠(VPA)诱导HL-60细胞分化过程中BRD4表达调控的分子机制。方法建立ATRA联合VPA诱导白血病细胞株HL-60的分化模型,瑞氏-吉姆萨(Wright-Gimesa)染色观察HL-60细胞形态,流式细胞术检测细胞表面分化抗原的表达,蛋白质印记从蛋白水平检测HL-60细胞经药物诱导24、48、72h后BRD4表达的变化。结果单独应用ATRA或VPA均能够明显抑制白血病细胞生长,诱导细胞分化,倒置显微镜下可观察到HL-60细胞向成熟粒细胞方向分化,细胞表面的分化抗原表达升高,联合诱导分化模型中细胞表面分化抗原表达升高更明显,两者均有统计学意义,在蛋白水平BRD4的表达逐渐降低,联合诱导分化模型中降低更明显,两者有统计学意义。结论 VPA可以明显的促进ATRA诱导白血病细胞的分化作用,BRD4基因的表达在随着分化程度的加强出现逐渐降低的趋势。Objective To investigate the effect of the molecular regulation mechanism of BRD4 in the mode of ATRA in combination with VPA induced differentiation in HL-60 cell. Methods ATRA in combination with VPA induced differentiation model of HL-60 cell line was established,morphology was observed by Wright-Gimesa staining,expression of cell surface differentiation antigen was detected by flow cytometry,through Western blot method to detect the expression of BRD4 protein level in acute promyelocytic leukemia cell （HL-60）induced by all-trans- retinoic acid from 24 h to 72 h. Results The results showed that the proliferation leukemia cells was obviously inhibited and the differentiation was induced by ATRA or VPA,expression of cell surface differentiation antigen was increased and induction differentiation model of cell surface differentiation antigen expression increased obviously,both of them had statistical significance.Decreases in protein expression level of BRD4,induction differentiation model was significantly lower,both of them had statistical significance. Conclusion VPA could promote the differentiation of HL-60 cells induced by ATRA,BRD4 expression level was reduced with the procession of differentiation.

关 键 词：白血病 诱导分化 全反式维甲酸 丙戊酸钠 BRD4 

分 类 号：R733.7[医药卫生—肿瘤]