TRAIL通路与原人参二醇对结肠癌的抑制作用相关。
TRAIL pathway is associated with inhibition of colon cancer by protopanaxadiol.
作者信息
Zhang Zhiyu, Li Zejuan, Wu Xiaohui, Zhang Chun-Feng, Calway Tyler, He Tong-Chuan, Du Wei, Chen Jianjun, Wang Chong-Zhi, Yuan Chun-Su
机构信息
Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA; Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL 60637, USA.
Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
出版信息
J Pharmacol Sci. 2015 Jan;127(1):83-91. doi: 10.1016/j.jphs.2014.11.003. Epub 2014 Nov 18.
Among important components of American ginseng, protopanaxadiol (PPD) showed more active anticancer potential than other triterpenoid saponins. In this study, we determined the in vivo effects of PPD in a mouse cancer model first. Then, using human colorectal cancer cell lines, we observed significant cancer cell growth inhibition by promoting G1 cell cycle redistribution and apoptosis. Subsequently, we characterized the downstream genes targeted by PPD in HCT-116 cancer cells. Using Affymetrix high density GeneChips, we obtained the gene expression profile of the cells. Microarray data indicated that the expression levels of 76 genes were changed over two-fold after PPD, of which 52 were upregulated while the remaining 24 were downregulated. Ingenuity pathway analysis of top functions affected was carried out. Data suggested that by regulating the interactions between p53 and DR4/DR5, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway played a key role in the action of PPD, a promising colon cancer inhibitory compound.
在西洋参的重要成分中，原人参二醇（PPD）比其他三萜皂苷显示出更具活性的抗癌潜力。在本研究中，我们首先在小鼠癌症模型中确定了PPD的体内作用。然后，使用人结肠癌细胞系，我们观察到通过促进G1期细胞周期重新分布和凋亡，PPD对癌细胞生长有显著抑制作用。随后，我们对PPD在HCT-116癌细胞中靶向的下游基因进行了表征。使用Affymetrix高密度基因芯片，我们获得了细胞的基因表达谱。微阵列数据表明，PPD处理后76个基因的表达水平变化超过两倍，其中52个上调，其余24个下调。我们对受影响的主要功能进行了 Ingenuity 通路分析。数据表明，通过调节p53与DR4/DR5之间的相互作用，肿瘤坏死因子相关凋亡诱导配体（TRAIL）通路在PPD（一种有前景的结肠癌抑制化合物）的作用中起关键作用。
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