丝裂原激活蛋白激酶信号转导系统对维甲酸诱导NB4细胞分化的影响

Effect of Mitogen-activated Protein Kinases on ATRA-induced Differentiation of NB4 Cells

本研究观察丝裂原活化蛋白激酶对全反式维甲酸(ATRA)诱导NB4细胞分化的影响并探讨其机制。采用MTT法测定细胞增殖活性,用流式细胞术分析细胞周期,NBT还原实验检测粒系分化,底物磷酸化法测定细胞外调节激酶(ERK)活性。结果显示:0.01-0.1μmol/L的ATRA呈时间和剂量依赖方式抑制NB4细胞增殖,并诱导NB4细胞向粒系分化;在这过程中ATRA激活ERK活性,ERK抑制剂PD98059能部分阻断ATRA的作用。p38MAPK的特异抑制剂SB203580与ATRA联合应用部分阻断了ATRA对细胞的生长抑制和诱导分化作用。结论:ATRA在诱导NB4细胞分化过程中激活ERK和P38MAPK途径,并且对该途径有依赖作用。

The aim of this study was to observe the effect of p38MAPK inhibitor SB203580 on ATRA-induced differentiation of NB4 ceils. The proliferation activity of ceils was assayed by MTT method, the cell cycle was detected by flow cytometry, the differentiation of NB4 cells into granulocytcs was measured by test of NBT reduction, the activity of extraccllular signal-regulated kinase （ERK） was detected by substrate phosphorylation. The results showed that the ATRA in 0.01 -01 μmol/L inhibited the proliferation of NB4 cells in time-and dose-depentent manner and induced the differentiation of NB4 cells into myeloid; the ATRA stimulated ERK activity in this process; ERK inhibitor PD98059 could partially block ATRA effect, specific inhibitor of p38MAPK, SB203580, combined with ATRA also could partially block the effects of ATRA on inhibition of NB4 growth and induction of differentiation. It is concluded that the ATRA stimulates ERK and p38MAPK pathway in the process inducing differentiation of NB4 cells, the ERK and P38MAPK may be necessary for the ATRA-induced differentiation in NB4 cells.