维甲酸诱导HL-60细胞分化中对细胞周期素依赖性激酶活性的影响

目的探讨维甲酸（ＲＡ）对ＨＬ６０细胞的增殖抑制和诱导分化作用与细胞周期素依赖性激酶（ＣＤＫ）活性变化的相关性。方法用５×１０－６ｍｏｌ／Ｌ全反式维甲酸（ＡＴＲＡ）或芳维甲（ＡＥ）处理ＨＬ６０细胞１～４天，在观察细胞生长、四氮唑蓝（ＮＢＴ）还原实验以及细胞周期分析的基础上，用组蛋白Ｈ１激酶活性分析技术检测ＣＤＫ２的活性，免疫沉淀法分析结合于ＣＤＫ２和ＣＤＫ４上的相应的细胞周期素（ｃｙｃｌｉｎ）Ｅ和Ｄ的量。结果ＨＬ６０细胞在ＡＴＲＡ或ＡＥ作用下，细胞增殖减慢，对ＮＢＴ的还原能力明显增强，９０％左右的细胞被阻滞在Ｇ１／Ｇ０期；在Ｇ１到Ｓ期转换过程中起关键作用的ｃｙｃｌｉｎＥ／ＣＤＫ２的活性显著下降，结合于ＣＤＫ４上的ｃｙｃｌｉｎＤ１的量减少。结论ＲＡ抑制ＨＬ６０细胞增殖并诱导其分化可能与ＣＤＫ２和ＣＤＫ４的活性下降有密切关系

Study of the role of cyclin dependent kinases (CDKs) in retinoic acid (RA) inducing HL 60 cell differentiation

OBJECTIVE: To investigate the role of CDKs in the RA inducing HL-60 cell differentiation. METHODS: The effects of all-trans retinoic acid (ATRA) and arotinoid ethylester(AE) at the dosage of 5 x 10(-6) mol/L on the proliferation and differentiation of HL-60 cells were examined by NBT reduction test and cytometry analysis. Meanwhile, histone H1 kinase assay was used to observe the changes of CDK2 activities in HL-60 cells treatment with ATRA and AE. The amounts of both cyclin E/CDK2 and cyclin D1/CDK4 complexes were observed with immunoprecipitates. RESULTS: Both ATRA and AE inhibited the growth of HL-60 cells, arrested cells in G1/G0 phase, and induced cells to differentiation. The activities of cyclin E/CDK2 and the amounts of cyclin D1/CDK4 complexes were decreased in ATRA- or AE-treated HL-60 cells. CONCLUSION: The effects of RA on the proliferation and differentiation of HL-60 cells may be associated with significant decreases in the activities of CDKs.