基于网络药理学和分子对接探讨瓜蒌-牛蒡子药对治疗乳腺癌的作用机制

Mechanism of action of Trichosanthes kirilowii Maxim-Fructus Arctii medicinal pairs for the treatment of breast cancer based on network pharmacology and molecular docking

目的通过网络药理学及分子对接技术研究瓜蒌-牛蒡子药对治疗乳腺癌的作用机制。方法应用中药系统药理学数据库与分析平台(TCMSP)筛选瓜蒌-牛蒡子药对的有效成分及药物作用靶点,通过GeneCard、PharmGkb、药物靶点数据库(TTD)、DrugBank数据库筛选乳腺癌的疾病靶点,将药物靶点与疾病靶点取交集后,应用STRING在线数据库和Cytoscape软件对交集靶点绘制蛋白质相互作用(PPI)网络获取核心靶点,并应用Cytoscape软件构建“药物-活性成分-靶点”网络获得药物的关键有效成分。应用R软件进行基因本体论(GO)及基因组百科全书(KEGG)富集分析,得到交集靶点的作用通路。最后应用AutoDock Tools、PyMOL软件,将筛选出的核心靶点及关键有效成分进行分子对接验证。结果通过筛选得到瓜蒌-牛蒡子药对治疗乳腺癌潜在核心靶点7个。通过GO富集分析共得到1801条结果,KEGG富集分析表明交集靶点共参与肿瘤坏死因子(TNF)、化学致癌-受体活化等146条通路。分子对接结果显示,瓜蒌-牛蒡子药对关键有效成分与核心作用靶点AKT1、Bcl-2、ESR1等可稳定结合。结论瓜蒌-牛蒡子药对可通过多种成分,作用于多个靶点,通过调控多条通路发挥治疗乳腺癌的作用。

Objective The Trichosanthes kirilowii Maxim-Fructus Arctii medicinal pairs in the treatment of breast cancer was studied by network pharmacology and molecular docking techniques.Methods Traditional Chinese Medicine Systerms Pharmacology Database and Analysis Platform(TCMSP)was used to screen the active ingredients and drug targets of the Trichosanthes kirilowii Maxim-Fructus Arctii medicinal pairs.Disease targets of breast cancer were screened through GeneCard,PharmGkb,Therapeutic Target Database(TTD)and DrugBank databases.After the intersection of drug target and disease target,STRING online database and Cytoscape software were applied to draw protein-protein interaction networks(PPI)for the intersection target to obtain the core target,and the drug-active ingredient-target network was constructed with Cytoscape software to obtain the key active ingredient of the drug.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed using R software,and the action pathways of intersection targets were obtained.Finally,AutoDock Tools and PyMOL were used to validate the selected core targets and key active components.Results Seven potential core targets of the Trichosanthes kirilowii Maxim-Fructus Arctii medicinal pairs were obtained through screening.A total of 1801 results were obtained by GO enrichment analysis,and KEGG enrichment analysis showed that intersection targets were involved in 146 pathways such as tumor necrosis factor(TNF)signaling pathway and Chemical carcinogenesis-receptor activation.Molecular docking results showed that the key effective ingredients and core targets AKT1,Bcl-2,ESR1 and so on could be stably combined.Conclusion The Trichosanthes kirilowii Maxim-Fructus Arctii medicinal pairs can act on multiple targets through a variety of ingredients,and play a role in the treatment of breast cancer by regulating multiple pathways.