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.
Publication types
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Clinical Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Antineoplastic Agents, Phytogenic / therapeutic use*
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Colorectal Neoplasms / drug therapy*
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Colorectal Neoplasms / genetics
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Colorectal Neoplasms / mortality
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Colorectal Neoplasms / pathology
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Computational Biology
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Drugs, Chinese Herbal / therapeutic use*
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Female
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Gene Expression Regulation, Neoplastic / drug effects*
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Gene Regulatory Networks / drug effects*
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Humans
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Lymphatic Metastasis
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Male
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Medicine, Chinese Traditional / methods
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Middle Aged
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Molecular Targeted Therapy
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Multivariate Analysis
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Neovascularization, Pathologic / genetics
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Neovascularization, Pathologic / metabolism
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Neovascularization, Pathologic / prevention & control*
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PPAR gamma / antagonists & inhibitors
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PPAR gamma / genetics
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PPAR gamma / metabolism
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Phosphatidylinositol 3-Kinase / genetics
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Phosphatidylinositol 3-Kinase / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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Receptor, ErbB-2 / antagonists & inhibitors
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Receptor, ErbB-2 / genetics
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Receptor, ErbB-2 / metabolism
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Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
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Receptors, Vascular Endothelial Growth Factor / genetics
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Receptors, Vascular Endothelial Growth Factor / metabolism
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Retinoid X Receptors / antagonists & inhibitors
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Retinoid X Receptors / genetics
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Retinoid X Receptors / metabolism
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Retrospective Studies
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Signal Transduction
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Survival Analysis
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Vascular Endothelial Growth Factor A / antagonists & inhibitors
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism
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src-Family Kinases / antagonists & inhibitors
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src-Family Kinases / genetics
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src-Family Kinases / metabolism
Substances
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Antineoplastic Agents, Phytogenic
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Drugs, Chinese Herbal
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PPAR gamma
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Phosphoinositide-3 Kinase Inhibitors
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Retinoid X Receptors
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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Phosphatidylinositol 3-Kinase
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ERBB2 protein, human
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Receptor, ErbB-2
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Receptors, Vascular Endothelial Growth Factor
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src-Family Kinases
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AKT1 protein, human
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Proto-Oncogene Proteins c-akt