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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DOI:
10.3892/ijo.32.5.975
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发表时间:
2008-05
影响因子:
5.2
通讯作者:
Xiaoji Luo;Chong-Zhi Wang;Jin Chen;Wen-Xin Song;Jinyong Luo;Ni Tang;Bai-Cheng He;Q. Kang;Yitao Wang;W. Du;T. He;C. Yuan
Xiaoji Luo;Chong-Zhi Wang;Jin Chen;Wen-Xin Song;Jinyong Luo;Ni Tang;Bai-Cheng He;Q. Kang;Yitao Wang;W. Du;T. He;C. Yuan
中科院分区:
医学2区
文献类型:
--
作者:
Xiaoji Luo;Chong-Zhi Wang;Jin Chen;Wen-Xin Song;Jinyong Luo;Ni Tang;Bai-Cheng He;Q. Kang;Yitao Wang;W. Du;T. He;C. Yuan

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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 Rg3 是西洋参中的皂苷之一,已被证明可以抑制肿瘤生长。在这项研究中,我们试图表征 HCT-116 人结直肠癌细胞中西洋参提取物靶向的下游基因。我们首先证明,与未蒸制的西洋参相比,在120℃蒸制2小时(简称S2h)的西洋参中Rg3的含量显着增加。 S2h和Rg3均对HCT-116细胞表现出抗增殖作用。使用包含超过 40,000 个基因和 EST 的 Affymetrix 高密度基因芯片,对 HCT-116 细胞的基因表达谱进行了分析。微阵列数据表明,经S2h或Rg3处理后,76个基因的表达水平发生显着变化,由此发现76个基因中52个上调,而其余24个下调。对受 S2h 和 Rg3 影响的顶级功能进行了独创性路径分析。受影响最大的途径是肝配蛋白受体途径。为了验证微阵列数据,对 6 个候选靶基因进行了定量实时 PCR,结果发现 3 个基因上调(AKAPA8L、PMPCB 和 PDE5A),3 个基因下调(PITPNA、DUS2L 和 RIC8A)。尽管需要进一步的研究来阐明其作用机制,但我们的研究结果应该会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 antiproliferative 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.