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Differentiation of PLZF-RARα-positive U937 leukemic cells induced by histone deacetylase inhibitor trichostatin A in combination with all-trans retinoic acid

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Author:
No author available
Journal Title:
JOURNAL OF THE FOURTH MILITARY MEDICAL UNIVERSITY
Issue:
15
DOI:
10.3321/j.issn:1000-2790.2007.15.003
Key Word:
PLZF;维甲酸;组蛋白去乙酰化酶;分化;白血病,早幼粒,急性

Abstract: 目的:研究组蛋白去乙酰化酶抑制剂曲古菌素A(TSA)和全反式维甲酸(ATRA)对PLZF-RARα阳性细胞的作用.方法:稳定转染PLZF-RARα基因的U937细胞(U937/PLZF)经TSA, ATRA作用一段时间后,Wright-Giemsa染色观察细胞形态,MTT法检测细胞生长和增殖状态,流式细胞仪检测细胞周期和细胞表面分化抗原CD11b,CD64,CD14等的表达,荧光免疫细胞化学染色检测融合蛋白表达,细胞化学染色和硝基蓝四氮唑(NBT)还原试验观察细胞功能分化情况.结果:U937/PLZF细胞在去除四环素条件培养后,PLZF-RARα表达明显增加.TSA (30 μg/L)联合ATRA (1 μmol/L)使U937/PLZF细胞核质比缩小,生长增殖受抑,S期细胞减少,CD11b表达增高,PLZF-RARα蛋白表达减弱,分布以胞核弥漫细小颗粒为主,细胞功能上的分化可能尚不成熟.结论:组蛋白去乙酰化酶抑制剂TSA联合ATRA可使U937/PLZF细胞发生部分分化.

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