Mesh ： Adult Aged Antineoplastic Agents, Phytogenic / therapeutic use Colorectal Neoplasms / drug therapy genetics mortality pathology Computational Biology Drugs, Chinese Herbal / therapeutic use Female Gene Expression Regulation, Neoplastic / drug effects Gene Regulatory Networks / drug effects Humans Lymphatic Metastasis Male Medicine, Chinese Traditional / methods Middle Aged Molecular Targeted Therapy Multivariate Analysis Neovascularization, Pathologic / genetics metabolism prevention & control PPAR gamma / antagonists & inhibitors genetics metabolism Phosphatidylinositol 3-Kinase / genetics metabolism Phosphoinositide-3 Kinase Inhibitors Proto-Oncogene Proteins c-akt / antagonists & inhibitors genetics metabolism Receptor, ErbB-2 / antagonists & inhibitors genetics metabolism Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors genetics metabolism Retinoid X Receptors / antagonists & inhibitors genetics metabolism Retrospective Studies Signal Transduction Survival Analysis Vascular Endothelial Growth Factor A / antagonists & inhibitors genetics metabolism src-Family Kinases / antagonists & inhibitors genetics metabolism

来  源：   DOI：10.1038/s41598-018-25500-x   PDF(Pubmed)

Abstract：
Increasing evidence has shown that Chinese herbal medicine (CHM) has promising therapeutic effects in colorectal cancer (CRC); however, the active ingredients and potential targets remain unclear. In this study, we aimed to investigate the relative molecular targets of the Chinese herbs that have been found effective in treating metastatic CRC (mCRC) based on clinical data and network pharmacology. In multivariate analysis CHM resulted an independent prognostic factor. The hazard ratio was 0.103 (95% confidence interval = 0.064-0.164; P < 0.001). Compared with the non-CHM group, the median survival time of the CHM group was also improved (40 versus 12 months; P < 0.001). Eighteen out of 295 herbs showed significant correlation with survival results (P < 0.05). Bioinformatics analysis indicated that the 18 herbs realize anti-CRC activity mainly through suppressing the proliferative activity of ERBB2, peroxisome proliferator-activated receptor gamma, and retinoid X receptor, suppressing angiogenesis via inhibition of VEGFR and VEGFA expression, inhibiting the phosphatidylinositol-3-kinase/AKT1 signaling pathway directly through SRC and AKT1, and reducing tumor necrosis factor-induced inflammation.
摘要：
越来越多的证据表明，中草药（CHM）在结直肠癌（CRC）中具有良好的治疗效果；然而，活性成分和潜在目标仍不清楚.在这项研究中,我们旨在基于临床数据和网络药理学研究已发现有效治疗转移性CRC(mCRC)的中药相关分子靶点.在多变量分析中，CHM是一个独立的预后因素。风险比为0.103（95％置信区间=0.064-0.164；P<0.001）。与非CHM组相比，CHM组的中位生存时间也得到改善(40对12个月;P<0.001).295种草药中有18种与生存结果显着相关（P<0.05）。生物信息学分析表明,18种中药主要通过抑制ERBB2、过氧化物酶体增殖物激活受体γ、和类维生素AX受体，通过抑制VEGFR和VEGFA表达来抑制血管生成，直接通过SRC和AKT1抑制磷脂酰肌醇-3-激酶/AKT1信号通路，减轻肿瘤坏死因子诱导的炎症反应。
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