7-乙酰基-鲁山冬凌草甲素诱导HL-60细胞周期阻滞及其机制研究
HL-60 cell cycle arrest induced by 7-acetyl-lushanrubescensin A and its mechanisms
查看参考文献15篇
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文摘
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目的 研究7-乙酰基-鲁山冬凌草甲素(7-acetyl-lushanrubescensin A,ARA)对人急性髓系白血病细胞株HL-60的细胞增殖和细胞周期的影响,并对其作用机制进行探讨.方法 MTT法检测ARA对HL-60细胞增殖的影响;在ARA作用HL-60细胞不同时间后,流式细胞仪检测细胞周期变化;Western印迹检测周期相关蛋白Rb、p(phospho)-Rb(ser795)、p-Rb(ser807/811),细胞周期蛋白(cyclin)D1、cyclin D3、cyclin E2、CDK4及CDK6的蛋白表达;流式细胞仪检测细胞内活性氧(ROS)水平.结果 ARA剂量依赖性地抑制HL-60细胞增殖,48 h的IC50为(1.96±0.08)μmol/L.ARA诱导HL-60细胞发生明显的细胞周期G0/G1阻滞,具有时间和浓度依赖性.机制研究显示ARA引起Rb总蛋白出现移行条带,并抑制p-Rb(ser795)位点磷酸化,显著抑制CDK4的蛋白表达,并部分降低cyclin D3和cyclin E2的表达水平,但对cyclin D1和CDK6的作用则不明显.此外,ARA显著增加HL-60细胞内ROS水平,而抗氧化剂N-乙酰半胱氨酸(NAC)能够阻断ARA诱导的ROS升高及细胞周期阻滞.结论 ARA能够明显抑制白血病细胞增殖,诱导细胞周期阻滞,其机制可能与抑制Rb活化和降低cyclin D3、cyclin E2和CDK4的表达水平相关,并且ROS在ARA介导的生物学效应中可能有重要作用. |
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其他语种文摘
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To exp lore the effect of 72acetyl2lushanrubescesin A (ARA) on cell p roliferation and cell cycle
of HL260 myeloid leukemia cell line, and to further investigate the mechanism of action. Methods MTT assaywas used to
assess the p roliferation of HL260 cells treated with ARA. After treatment of HL260 cells with ARA of different durations,
cell cycle changes were determined by flow cytometry. The p rotein exp ression of Rb, p ( phospho) 2Rb ( ser795 ) , p2Rb
( ser807 /811) , cyclin D1, cyclin D3, cyclin E2, CDK4 and CDK6 were detected byWestern blot. The intracellular reac2
tive oxygen species (ROS) levelwasmeasured by flow cytometry. Results ARA inhibited the p roliferation of HL260 cells
in a concentration2dependentmanner, with an IC50 of (1. 96 ±0. 08)μmol/L at 48 h. ARA induced significant G0 /G1
phase arrest of HL260 cells in a time2and concentration2dependent manner. Studies on the mechanisms underlying these
effects indicated that treatment with ARA induced the rap idly migrating band of total Rb p rotein, and reduced the pRb
phosphorylation on ser795. Furthermore, ARA markedly inhibited the p rotein exp ression of CDK4, and partially decreased ex2
p ression of cyclin D3 and cyclin E2, but had no effect on cyclin D1 and CDK6. In addition, ARA significantly increased the
intracellular ROS level of HL260 cells, whereas antioxidantNAC blocked the ROS p roduction and cell cycle arrest induced by
ARA. Conclusion ARA can significantly inhibit p roliferation and induce cell cycle arrest of leukemia cells. Themechanisms
underlying these effectsmay be related to inhibition of pRb phosphorylation and down2regulation of cyclin D3, cyclin E2, and
CDK4 p rotein exp ression. Furthermore, ROS p roduction may p lay an important role in the biological effects of ARA. |
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来源
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军事医学科学院院刊
,2010,34(2):156-159 【核心库】
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关键词
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7-乙酰基-鲁山冬凌草甲素
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HL-60细胞
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细胞增殖
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细胞周期阻滞
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活性氧
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白血病
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地址
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1.
中国药科大学临床药学教研室, 江苏, 南京, 210009
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军事医学科学院放射与辐射医学研究所, 北京, 100850
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中国科学院昆明植物研究所, 云南, 昆明, 650204
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语种
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中文 |
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文献类型
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研究性论文 |
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ISSN
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1000-5501 |
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学科
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肿瘤学 |
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文献收藏号
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CSCD:3869354
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