Apigenin inhibits hepatoma cell growth through alteration of gene expression patterns
Apigenin inhibits hepatoma cell growth through alteration of gene expression patterns
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DOI：
10.1016/j.phymed.2010.08.006
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发表时间：
2011-03-15
期刊：
影响因子：
7.9
通讯作者：
Zhang, Shu-Hui
中科院分区：
文献类型：
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作者：
Cai, Jing;Zhao, Xiang-Li;Zhang, Shu-Hui
芹菜素是一种常见的植物黄酮类化合物，已被证明具有抗肿瘤作用，但其潜在的分子机制仍不完全清楚。在本研究中，我们研究了芹菜素对人肝癌HuH7细胞体外增殖、细胞周期分布、细胞凋亡和集落形成的影响，以及对HuH7细胞体内致瘤性的影响。为了更深入地了解芹菜素的作用机制，我们使用包含41,000个基因的cDNA微阵列(安捷伦全人类基因组寡核苷酸微阵列)对芹菜素处理的Huh7细胞进行了全基因组表达谱分析。选择了10个差异表达最高的基因(~gt；=5倍变化)，通过定量RT-PCR和Western印迹分析进行进一步评估。值得注意的是，与载体对照组相比，芹菜素(5-20微克/毫升)显著抑制HuH7细胞的增殖和集落形成，且呈剂量依赖关系。随着细胞生长速度的下降，芹菜素处理的细胞出现G2/M期停滞，细胞凋亡率增加。此外，与对照组相比，芹菜素(50微克/鼠/天)显著延缓了Huh7细胞来源的异种移植(p<；0.05)。基因表达谱分析表明，芹菜素上调了1336个基因，下调了428个基因。定量聚合酶链式反应和Western印迹结果进一步证实，IL-4受体和泛素特异性蛋白水解酶18表达下调，SLC27A3和趋化因子(C-C基序)受体2表达上调。总之，芹菜素对肝癌细胞的生长具有抑制作用，这种抑制作用可能是通过改变基因表达谱来实现的。(C)2010年爱思唯尔股份有限公司。版权所有。
Apigenin, a common plant flavonoid, has been shown to possess anti-tumor properties; however, the underlying molecular mechanisms are still not completely understood. In the present study, we investigated the effects of apigenin on human hepatoma Huh7 cell proliferation, cell cycle distribution, apoptosis, and colony formation in vitro, as well as on the tumorigenicity of Huh7 cells in vivo. To get more insight into the mechanism of apigenin action, we performed genome-wide expression profiling of apigenin-treated Huh7 cells using cDNA microarrays (Agilent Whole Human Genome Oligo Microarray) that contain 41,000 genes. Ten of the most differentially expressed genes (>= 5-fold changes) were selected for further evaluation by quantitative RT-PCR (qPCR) and Western blot analyses. Notably, apigenin (5-20 mu g/ml) remarkably inhibited Huh7 cell proliferation and colony formation as compared to the vehicle control, which was in a dose-dependent manner. Accompanying with the decreased growth, apigenin-treated cells showed a cell cycle arrest at G2/M phase and an increased rate of apoptosis. Moreover, the xenografts derived from Huh7 cells were significantly (p < 0.05) retarded by the delivery of apigenin (50 mu g/mouse/day) relative to the control counterparts. Gene expression profile analysis revealed that 1336 genes were up-regulated and 428 genes were down-regulated by apigenin. The down-regulation of interleukin-4 receptor and ubiquitin specific protease 18 and the up-regulation of SLC27A3 and chemokine (C-C motif) receptor 2 were further confirmed by the qPCR and Western blot results. In conclusion, apigenin exhibits inhibitory effects on hepatoma cell growth, which is likely mediated through alteration of gene expression profiles. (C) 2010 Elsevier GmbH. All rights reserved.