基于网络药理学和分子对接探讨斑蝥复方制剂治疗宫颈癌的作用机制

Exploring the mechanism of cantharidin compound reparation for treating cervical cancer based on network pharmacology and molecular docking verification

目的:基于网络药理学和分子对接技术,探讨斑蝥复方制剂治疗宫颈癌的生物活性成分以及潜在作用机制。方法:从中药系统药理学数据库分析平台(TCMSP)和文献筛选确定相应的活性成分和药物靶点,通过Genecards、OMIM数据库收集宫颈癌靶点。运用STRING数据库借助Cytoscape3.8.2软件构建PPI网络图和“药物-成分-靶点-通路”网格。应用Metascape进行GO(Gene ontology)功能和KEGG(Kyoto encyclopedia of genes and genomes)通路富集分析。采用Autoduck软件对具有代表性的活性成分和作用靶点进行分子对接验证。结果:通过筛选共确定34种活性成分和211个药物靶点与1218个疾病靶点,交汇得到110个交集靶点,其中核心靶点包括TP53、AKT1、MAPK1、TNF等;KEGG富集分析显示核心靶点主要与癌症途径、IL-17信号通路、PI3K-Akt信号通路等密切相关。分子对接结果表明JUN和HSP90AA1与活性成分有着较好的结合亲和力。结论:本研究初步揭示了斑蝥复方制剂通过多组分、多靶点、多通路治疗宫颈癌的机制,为后续斑蝥复方制剂治疗宫颈癌的分子机制及新药的开发提供新的思路。

Objective:This study aimed to investigate the bioactive components and potential mechanisms of cantharidin compound reparation(CCR)for cervical cancer(CC)treatment based on network pharmacology combined with molecular docking.Methods:The corresponding active ingredients and their target proteins were screened from Traditional Chinese Medicine System Pharmacology(TCMSP)database and lectures.Meanwhile,the disease-associated targets were retrieved from Genecards and OMIM databases.The protein-protein interaction(PPI)network and drugs-components-targets-pathways network were conducted through STRING network platform and Cytoscape software.Moreover,The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed by Metascape.Finally,AutoDuck Tools was utilized to perform molecular docking verification of the representative active components and action targets.Results:The results showed that a total of 34 active ingredients,211 drug targets and 1218 disease-associated targets were identified,of which 110 intersection targets were obtained.The top ten key targets were screened out,including TP53,AKT1,MAPK1,TNF and so on.The KEGG enrichment manifested that the core targets were closely related to pathways in cancer,IL-17 signaling pathway and P13K-Akt signaling pathway.In addition,molecular docking methods confirmed the high affinity between the active components and hub targets like JUN,HSP90AAI.Conclusion:This study preliminarily demonstrated that cantharidin compound preparation exerted a therapeutic effect for cervical cancer via multicomponent,multitarget,and multisignal pathway,which shed new light on the molecular mechanism of CCR against CC and new drugs development.