Abstract:

Objective　To investigate the target and mechanism of radix trichosanthis in the treatment of lung cancer based on network pharmacology and molecular docking. Methods　The search period was up to July 2022. The active ingredients of radix trichosanthis were selected using the TCMSP and TCMID databases combined with the PubChem database. The potential targets of active ingredients were obtained using the TCMSP, TCMID, and SwissTargetPrediction databases. The GeneCards, OMIM, TTD, and DrugBank databases were searched to collect the targets of lung cancer. The drugs were intersected with disease targets and a Venn diagram was drawn using the online web site Venny 2.1. The common target protein-protein interaction network was drawn using the String database. The "drug-active ingredient-disease-target" network diagram was constructed through Cytoscape 3.8.2 software. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of common targets were performed using Metascape database. Molecular docking verification was performed using Autodock software. Results　Through screening, 28 active ingredients and 201 action targets were obtained from radix trichosanthis. A total of 1 645 lung cancer targets were retrieved from the four major disease databases. There were 37 intersecting targets between the drug and disease. According to the Degree value, estrogen receptor 1 (ER1), signal transduction and transcriptional activator 3 (STAT3), and epidermal growth factor receptor (EGFR) were determined as the core targets. GO enrichment analysis found that radix trichosanthis might treat lung cancer by regulating gland development, cell proliferation, cell adhesion, receptors, enzymes, and activities of proteins. The KEGG pathway enrichment analysis revealed that radix trichosanthis might act on chemical oncogenic receptor activation, pathways in cancer, hypoxia-inducing factor 1 (HIF-1) signaling pathway, and microRNAs and proteoglycans in cancer. Molecular docking results showed that the binding activity of key small molecule compounds to the core target was significant. Conclusion　Radix trichosanthis plays a role in the treatment of lung cancer through multi-target and multi-pathway mechanisms, laying a foundation for subsequent experiments and clinical applications.

Key words:

Lung cancer, Radix trichosanthis, Network pharmacology, Molecular docking, Small molecular compound, Mechanism of action,  , Investigation

摘要：

目的　基于网络药理学和分子对接的方法探讨天花粉治疗肺癌的作用靶点及机制。方法　检索时限为建库至2022年7月。采用中药系统药理学数据库和分析平台（TCMSP）、中医药综合数据库（TCMID）结合PubChem数据库相关文献筛选出天花粉的活性成分，通过TCMSP、TCMID、SwissTargetPrediction数据库获取活性成分的潜在靶点；检索GeneCards、人类孟德尔遗传综合数据库（OMIM）、TTD、DrugBank数据库收集肺癌疾病靶点；利用线上网站Venny 2.1将药物与疾病靶点取交集并绘制韦恩图；应用String数据库绘制交集靶点的蛋白互作网络；使用Cytoscape 3.8.2软件构建“药物-活性成分-疾病-靶点”网络图；运用Metascape数据库对共同靶点进行基因本体（GO）富集化分析和京都基因和基因组数据库（KEGG）通路富集分析；采用Autodock软件进行分子对接验证。结果　天花粉通过筛选得到活性成分28种，201个作用靶点；检索4大疾病数据库共获取肺癌靶点1 645个；药物与疾病共有37个交集靶点；根据连接度（degree）值大小，确定雌激素受体1（ER1）、信号转导和转录激活因子3（STAT3）、表皮生长因子受体（EGFR）为核心靶点。GO富集分析发现天花粉可能通过调节腺体发育、细胞增殖、细胞黏附、酶、受体、蛋白质的活性等治疗肺癌。KEGG通路富集分析显示天花粉可能作用于化学致癌受体激活、癌症通路、缺氧诱导因子1（HIF-1）信号通路、癌症中的微RNA、蛋白聚糖等发挥作用。分子对接结果显示，关键小分子化合物与核心靶点的结合活性显著。结论　天花粉通过多靶点、多通路机制发挥治疗肺癌的作用，为后续实验和临床应用奠定基础。

关键词:

肺癌, 天花粉, 网络药理学, 分子对接, 小分子化合物, 作用机制, 探讨