乌苯美司增强全反式维甲酸诱导急性早幼粒细胞白血病细胞分化的体外研究  

Experimental study of the enhancement effect of aminopeptidase N inhibitor ubenimex on the differentiation induction activity of all-trans-retinoic acid in acute promyelocytic leukemia cells and its mechanism

作　　者：钱习军[1] 林茂芳[1] 

机构地区：[1]浙江大学医学院第一附属医院血液科,杭州310003

出　　处：《中华血液学杂志》2006年第7期445-448,共4页Chinese Journal of Hematology

摘　　要：目的探讨氨肽酶 N 抑制剂乌苯美司(ubenimex)对全反式维甲酸(ATRA)诱导人急性早幼粒细胞白血病(APL)细胞分化的影响及可能机制。方法采用流式细胞术检测细胞表面分化抗原 CD11b,四氮唑蓝(NRT)还原实验检测细胞分化;Western blot 法检测细胞 c-Myc、ERK_(1/2)及 p-ERK_(1/2)、p38MAPK 及 p-p38MAPK 蛋白表达。结果 ubenimex 单独应用对 NB4细胞的 NBT 还原能力及 CD11b 表达无明显影响,但 ubenimex 能增强 ATRA 诱导 NB4细胞的 NBT 还原能力及 CD11b 的表达。100 μg/ml ubenimex 能增强10 nmol/L ATRA 诱导原代 APL 细胞的 NBT 还原能力。100μg/mlubenimex 增强10 nmol/L ATRA 下调 NB4细胞 c-Myc 蛋白的表达;抑制10 nmol/L ATRA 引起的 NB4细胞的 p38MAPK 磷酸化。结论 ubenimex 能够增强 ATRA 对 APL 细胞的诱导分化作用,可能与抑制p38MAPK 的磷酸化及对原癌基因 c-Myc 表达的调控有关。Objective To investigate the effect of aminopeptidase N inhibitor ubenimex on differentiation induction of all-trans-retinoic acid （ ATRA ） in acute promyelocytic leukemia （ APL ） cells and its mechanism. Methods The expression of CDllb was analyzed by flow cytometry and nitroblue-tetrazolium （NBT） reduction assay was performed to determine the cell differentiation of APL cells. The expressions of c-Myc, ERK1/2, p38MAPK protein and the phosphorylation of ERK1/2, p38MAPK protein in NB4 cells were detected by Western blot assay. Results Ubenimex alone induced no significant changes in NBT reduction activity and CD11 b expression but potentiated the differentiation induction activity of ATRA in APL cells. 100 μg/ml of ubenimex could enhance the NBT reduction activity induced by 10 nmol/L of ATRA, intensify the down-regulation of c-Myc protein expression and inhibit the phosphorylation of p38MAPK protein induced by 10 nmol/L of ATRA in NB4 cells. Conclusions Ubenimex could potentiate ATRA induced differentiation in APL cells, which may be correlated with the inhibition of p38 MAPK protein phosphorylation and regulation of c-Myc protein expression.

关 键 词：氨肽酶抑制剂类 维甲酸 白血病 早幼粒细胞 急性 细胞分化 

分 类 号：R733.7[医药卫生—肿瘤]