| 摘要: |
| 目的:基于网络药理学、生物信息学和分子对接探讨紫草治疗结直肠癌的作用机制。方法：通过中药系统药理学数据库与分析平台筛选紫草的有效化学成分，预测化合物的相应潜在靶基因，构建靶点网络，搜索和过滤结直肠癌靶点，取药物-疾病靶点交集，构建蛋白质-蛋白质相互作用（Protein-Protein Interaction，PPI）网络及活性成分-靶点-通路相互作用网络。微生信平台进行基因本体（gene ontology，GO）功能与京都基因和基因组数据库（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集分析，进一步探索有效基因并进行预后分析，最后进行分子对接。结果：紫草和结直肠癌产生196个交叉目标。紫草素、乙酰紫草素、谷甾醇、亚油酸乙脂是主要活性物质，而丝氨酸/苏氨酸蛋白激酶1（Serine/Threonine-Protein Kinase 1，AKT1）、信号转导及转录激活因子3（Signal Transducer and Activator of Transcription 3，STAT3）、过氧化物酶体增殖物激活受体γ（Peroxisome Proliferator-Activated Receptor Gamma，PPARG）、表皮生长因子受体（Epidermal Growth Factor Receptor，EGFR）和SRC原癌基因，非受体型酪氨酸激酶（SRC Proto-Oncogene，Non-Receptor Tyrosine Kinase，SRC）是主要靶点。GO功能分析得出氧化应激的反应、对类固醇激素的反应等生物过程，磷酸酶绑定、核受体活性等分子功能，膜筏、囊腔等细胞组分。KEGG通路富集分析结果涉及癌症的途径、表皮生长因子受体信号通路（EGFR signaling pathway）、化学致癌受体活化等通路。生物信息学分析筛选出有效基因AKT1、STAT3、PPARG、EGFR和SRC。分子对接结果表明其中活性成分紫草素与关键靶点SRC的对接结合力最强，为-30.54 kJ/mol。结论：紫草可以通过多个成分、多个靶点和多个通路治疗结直肠癌，初步揭示了紫草治疗结直癌的有效成分和分子机制。 |
| 关键词: 结直肠癌 紫草 分子对接 网络药理学 生信分析 |
| DOI： |
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| Mechanism of action of arnebia root in treatment of colorectal cancer：A study based on network pharmacology，bioinformatics，and molecular docking |
| WANG Juanjuan,LI Canyu,YANG Xu |
| (Guizhou University of Traditional Chinese Medicine，Guiyang 550025，Guizhou，China) |
| Abstract: |
| Objective：To investigate the mechanism of action of arnebia root in the treatment of colorectal cancer based on network pharmacology，bioinformatics，and molecular docking.Methods：Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to identify the effective chemical components of arnebia root，and their corresponding target genes were predicted to construct a target network.The targets of colorectal cancer were searched and screened，and the drug-disease intersecting targets were obtained.A protein-protein interaction network and an active component-target-pathway interaction network were constructed.Weishengxin platform was used for the gene ontology (GO) functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to further explore effective genes and perform a prognostic analysis，and then molecular docking was performed.Results：There were 196 intersecting targets between arnebia root and colorectal cancer.Shikonin，acetyl shikonin，sitosterol，and ethyl linoleate were the main active substances，and AKT serine/threonine kinase 1，signal transducer and activator of transcription 3，peroxisome proliferator-activated receptor gamma，epithelial growth factor receptor，and SRC proto-oncogene，non-receptor tyrosine kinase were the main targets.The GO functional enrichment analysis obtained the biological processes such as oxidative stress reaction and reaction to steroid hormones，the molecular functions such as phosphatase binding and nuclear receptor activity，and the cellular components such as membrane rafts and cystic cavities.The KEGG pathway enrichment analysis obtained the pathways such as cancer-related pathways，the epidermal growth factor receptor signaling pathway，and chemical carcinogenesis-receptor activation.The bioinformatics analysis identified the effective genes of AKT1，STAT3，PPARG，EGFR，and SRC.The results of molecular docking showed that among the active components of arnebia root，shikonin showed the strongest binding force of-30.54 kJ/mol to the key target SRC.Conclusion：Arnebia root exerts a therapeutic effect on colorectal cancer through multiple components，targets，and pathways，which preliminarily reveal the effective components and molecular mechanism of arnebia root in the treatment of colorectal cancer. |
| Key words: arnebia root colorectal cancer molecular docking network pharmacology bioinformatics analysis |
