Induction of myelogenous leukemia cells with histone deacetylase inhibitors through down-regulating the Daxx protein expression

Induction of myelogenous leukemia cells with histone deacetylase inhibitors through down-regulating the Daxx protein expression
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组蛋白脱乙酰酶抑制剂通过下调 Daxx 蛋白表达诱导骨髓性白血病细胞

DOI:
10.1007/s11596-009-0504-7
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发表时间:
2009-10
期刊:
Journal of Huazhong University of Science and Technology - Medical Science
影响因子:
--
通讯作者:
Deng, J.
Deng, J.
中科院分区:
其他
文献类型:
--
作者:
Wu, X.;Liu, W.;Li, C.;Zhou, J.;Tian, Y.;Deng, J.

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研究了组蛋白去乙酰化酶(HDAC)抑制剂丁酸钠(NaB)和曲古霉素A (TSA)对人白血病细胞体外凋亡的影响及其分子机制。实验分为5组:对照组、NaB组、TSA组、NaB+Z-VAD-FMK组和TSA+Z-VAD-FMK组。形态学分析和流式细胞术检测细胞凋亡率。Western blot检测Daxx、Bcl-2、Bcl-xl蛋白的表达。NaB和TSA均能诱导HL-60和K562细胞凋亡,Z-VAD-FMK能显著降低HDAC抑制剂诱导的细胞凋亡。HDAC抑制剂可下调Daxx蛋白的表达,但对Bcl-2和Bcl-xl蛋白的表达无显著影响。结果表明,NaB和TSA通过下调体外Daxx蛋白的表达诱导人白血病细胞明显的caspase依赖性凋亡。
The effects of two different histone deacetylase (HDAC) inhibitors, sodium butyrate (NaB) and trichostatin A (TSA),on apoptosis of human leukemic cellsin vitroand the molecular mechanisms were investigated. The experiments were divided up 5 groups: control group, NaB group, TSA group, NaB+Z-VAD-FMK group and TSA+Z-VAD-FMK group. The apoptosis rate was determined by morphological analysis and flow cytomytry. The expression of Daxx, Bcl-2, and Bcl-xl proteins was detected by Western blot. NaB and TSA could induce the apoptosis of HL-60 and K562 cells, and Z-VAD-FMK caused a marked decrease in apoptosis induced by HDAC inhibitors. HDAC inhibitors could down-regulate the expression of Daxx protein, but had no significant influence on the expression of Bcl-2 and Bcl-xl proteins. The results suggested that NaB and TSA induce distinct caspase-dependent apoptosis of human leukemic cells through down-regulating the expression of Daxx proteinin vitro.
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