论文部分内容阅读
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 and possible mechanism of aminopeptidase N inhibitor ubenimex on differentiation of human acute promyelocytic leukemia (APL) cells induced by all-trans retinoic acid (ATRA). Methods Flow cytometry was used to detect cell surface differentiation antigen CD11b and NRT reduction assay. Western blot was used to detect the expression of c-Myc, ERK_ (1/2) and p-ERK_ (1/2) , P38MAPK and p-p38MAPK protein expression. Results ubenimex alone had no effect on NBT cell proliferation and CD11b expression, but ubenimex enhanced NBT cell proliferation and CD11b expression induced by ATRA. 100 μg / ml ubenimex enhanced the NBT reduction ability of 10 nmol / L ATRA-induced primary APL cells. 100 microg / mlubenimex enhanced 10 nmol / L ATRA down-regulated c-Myc protein expression in NB4 cells and inhibited p38 MAPK phosphorylation induced by 10 nmol / L ATRA in NB4 cells. Conclusion ubenimex can enhance the differentiation of APL cells induced by ATRA, which may be related to the inhibition of p38MAPK phosphorylation and the regulation of c-Myc expression.