乌索酸诱导人急性早幼粒白血病细胞株HL-60分化的机制
Mechanism of the differentiation of human leukemia cell line HL-60 induced by ursolic acid
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摘要: 研究在乌索酸诱导的人急性早幼粒白血病细胞株HL-60分化过程中PI3K/Akt信号通路的调控作用。乌索酸作用HL-60细胞96 h后,通过形态学观察,四唑氮兰(NBT)还原实验等研究发现乌索酸能诱导HL-60细胞发生单核分化;Western blotting结果表明乌索酸能激活PI3K/Akt信号通路,上调通路关键蛋白——Thr308和Ser473两个位点磷酸化的Akt,且通过免疫荧光实验检测到通路激活过程中发生Akt的核迁移;另外,为进一步证明分化与PI3K/Akt通路的相关性,采用PI3K特异性抑制剂LY294002,结果发现抑制剂作用后乌索酸的诱导分化作用消失。因此,乌索酸能够诱导HL-60细胞向单核方向分化,其作用机制可能是通过激活PI3K/Akt通路,从而达到分化诱导作用。
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关键词:
- 乌索酸 /
- 分化 /
- 急性早幼粒白血病 /
- HL-60 /
- PI3K-Akt通路
Abstract: The effects and mechanism of ursolic acid (UA) on the differentiation of human leukemia cell line HL-60 was investigated in this study .The morphology of HL-60 cells changed after 96 h treatment with UA,and the NBT reduction assay preliminarily suggested monocytic differentiation of the cells. Akt was phosphorylated at Thr308 and Ser473 in HL-60 cells after treatment with UA and the nuclear translocation of active Akt was observed using immunofluorescence microscopy. A specific PI3K inhibitor LY294002 was utilized to further explore the role of PI3K/Akt pathway during the process of differentiation,and it was found that UA-induced differentiation was blocked by LY294002. In conclusion,UA could induce monocytic differentiation of HL-60 cells through the activation of PI3K/Akt signaling pathway.-
Keywords:
- ursolic acid (UA) /
- differentiation /
- aucute promyelocytic /
- leukemia /
- HL-60 /
- PI3K/Akt signaling pathway
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