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.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2006年第7期445-448,共4页
Chinese Journal of Hematology
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
Inhibitor, aminopeptidase
Retinoic acid
Leukemia, promyelocytic, acute
Cell differentiation
