小剂量As_2O_3体外诱导HL-60细胞发生非终末分化分子机制的研究  

The molecular mechanisms of As_2O_3- induced un-terminal differentiation of HL-60 cells

作　　者：白厚桥[1,2,3,4] 郭铁军[1,2,3,4] 温培娥[1,2,3,4] 任海全[1,2,3,4] 张玉昆[1,2,3,4] 唐天华[1,2,3,4] 张灏[1,2,3,4] 毕高峰[1,2,3,4] 刘佳宁[1,2,3,4] 姜国胜[1,2,3,4] 

机构地区：[1]山东省医学科学院基础医学研究所,济南250062 [2]山东省现代医用药物与技术重点实验室 [3]山东省医药卫生肿瘤免疫与中药免疫重点实验室 [4]山东省医学科学院血液肿瘤防治研究中心

出　　处：《国际肿瘤学杂志》2006年第5期386-390,共5页Journal of International Oncology

基　　金：山东省优秀中青年科学家基金资助项目(03BS033)

摘　　要：目的探讨增强子结合蛋白C／EBPs在小剂量三氧化二砷(As_2O_3)诱导HL-60细胞发生非终末分化中的作用。方法采用瑞式染色观察细胞形态,WST1实验测定细胞增殖变化,测定和分析细胞周期,NBT还原实验测定细胞分化状态,RT-PCR方法检测C／EBPα和C／EBPε的 mRNA表达。结果HL-60细胞经全反式维甲酸(ATRA)作用24 h后,随着细胞分化的发生, C／EBPε mRNA的表达明显增加,C／EBPα mRNA的表达降低。HL-60细胞经As_2O_3作用24 h后, C／EBPα mRNA的表达降低,C／EBPε mRNA的表达轻微增加。结论经As_2O_2和ATRA诱导后不同分化状态HL-60细胞,C／EBPα mRNA的表达降低,二者差异无显著意义;C／EBPε的表达差异较大(P<0．05),二者差异有显著意义。小剂量As_2O_3诱导HL-60细胞发生非终末分化可能是由于C／EBPε不能持续表达升高引起的。Objective To approach the effect of CCAAT/enhancer binding proteins （C/EBPs） on un-terminal differentiation of HL-60 cells after treatment with Arsenic Trioxide （As2O3 ）. Methods The changes of cell morphology were observed by Wright staining, the alteration in the cell proliferation was determined by WST1 experiment and the NBT reduction assay was used to detect the differentiation condition of cells, determination and analysis cell cycle. The expressions of C/EBPα and C/EBPε mRNA in HL-60 cells exposed to ATRA and As2O3 were assayed by semi-quantitative RT-PCR. Results It was found that ATRA could up-regulate the mRNA expression of C/EBPε obviously, but down-regulate the mRNA expression of C/EBPα ,As2O3 could up-regulate the mRNA expression of C/EBPε lightly, downregulate the expression of C/EBPct. Conclusion Both of ATRA and As2O3 can down-regulate the mRNA expression of C/EBPα,but there is no significant difference between these two groups,ATRA and As2O3 can up-regulate the mRNA expression of C/EBPε,with significant differences（ P 〈 0. 05）. As2O3 induces un-terminal differentiation of HL-60 cells possibly duo to not up-regulating of C/EBPε expression obviously .

关 键 词：砷剂 维甲酸 增强子结合蛋白 HL-60细胞 

分 类 号：R733.7[医药卫生—肿瘤]