Characterization of gene expression regulated by American ginseng and ginsenoside Rg3 in human colorectal cancer cells
Characterization of gene expression regulated by American ginseng and ginsenoside Rg3 in human colorectal cancer cells
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人结直肠癌细胞中西洋参和人参皂苷 Rg3 调控基因表达的表征
DOI：
10.1007/978-3-540-77385-6
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发表时间：
2008-05-01
影响因子：
5.2
通讯作者：
Yuan, Chun-Su
中科院分区：
文献类型：
--
作者：
Luo, Xiaoji;Wang, Chong-Zhi;Yuan, Chun-Su
西洋参（Panax quinquefolius L.，五加科）具有抗癌潜力，是美国最常用的草药之一。人参皂苷Rg 3是西洋参中的皂苷之一，已显示出抑制肿瘤生长。在这项研究中，我们试图描述西洋参提取物在HCT-116人结直肠癌细胞中靶向的下游基因。我们首次证明了西洋参在120 ℃蒸2小时（简称S2 h）的人参中Rg 3的含量显着增加时，与未蒸的人参。S2 h和Rg 3均对HCT-116细胞有抑制增殖作用。利用包含40，000多个基因和ESTs的Affyoung高密度基因芯片，分析HCT-116细胞的基因表达谱。微阵列数据表明，在用S2 h或Rg 3处理后，76个基因的表达水平显著改变，由此发现76个基因中的52个上调，而其余24个下调。进行了受S2 h和Rg 3两者影响的顶部功能的分析。最有效的途径是肝配蛋白受体途径。为了验证微阵列数据，对6个候选靶基因进行定量实时PCR，由此发现3个基因上调（AKAPA 8L、PMPCB和PDE 5A），3个基因下调（PITPNA、DUS 2L和RIC 8A）。虽然需要进一步的研究来阐明作用机制，但我们的发现应该扩大对西洋参作为抗癌剂的分子框架的理解。
American ginseng (Panax quinquefolius L., Araliaceae) possesses anti-cancer potential and is one of the most commonly used herbal medicines in the United States. Ginsenoside Rg3, one of the saponins in American ginseng, has been shown to inhibit tumor growth. In this study, we sought to characterize the downstream genes targeted by American ginseng extracts in HCT-116 human colorectal cancer cells. We first demonstrated that the content of Rg3 in American ginseng steamed at 120 degrees C for 2 h (referred to as S2h) was significantly increased when compared with that of the unsteamed ginseng. Both S2h and Rg3 exhibited anti-proliferative effects on HCT-116 cells. Using the Affymetrix high density genechips containing more than 40,000 genes and ESTs, the gene expression profiling of HCT-116 cells were assayed. Microarray data indicated that the expression levels of 76 genes were changed significantly after treatment with S2h or Rg3, whereby it was found that 52 of the 76 genes were up-regulated while the remaining 24 were down-regulated. Ingenuity Pathways Analysis of top functions affected by both S2h and Rg3 were carried out. The most effected pathway is the Ephrin receptor pathway. To validate the microarray data, quantitative real-time PCR of six candidate target genes was conducted, whereby it was found that three genes were up-regulated (AKAPA8L, PMPCB and PDE5A) and three were down-regulated (PITPNA, DUS2L and RIC8A). Although further studies are needed to elucidate the mechanisms of action, our findings should expand the understanding of the molecular framework of American ginseng as an anti-cancer agent.