基于网络药理学探究胃安散治疗胃癌的作用机制

Exploring the Mechanism of Action of Wei-An Powder in Treating Gastric Cancer Based on Network Pharmacology

  • 摘要:
    目的 基于网络药理学和实验验证探究胃安散治疗胃癌的作用机制。
    方法 通过TCMSP、TCM-ID等数据库筛选胃安散的活性成分,预测胃安散的作用靶点;通过GeneCards、OMIM等数据库筛选胃癌的潜在靶点;将活性成分作用靶点与胃癌潜在靶点取交集后,通过String11.0数据库构建蛋白质互作网络,并将PPI网络导入Cytoscape 3.9.0软件筛选核心靶点;通过DAVID数据库进行GO功能与KEGG代谢通路富集分析以预测作用机制;通过Pyrx软件进行分子对接验证。采用胃癌细胞AGS,通过ELISA、qPCR以及Western blot实验验证网络药理学的分析结果。
    结果 共筛选得到胃安散活性成分作用靶点341个,胃癌潜在靶点7 031个,取交集后共得到胃安散治疗胃癌靶点743个,其中核心靶点是TP53、AKT1、TNF和IL-6等。GO和KEGG富集分析显示胃安散主要通过癌症通路、PI3K-Akt信号通路、MAPK信号通路和凋亡通路等发挥作用。分子对接结果提示,核心靶点与活性成分均具有较高的结合活性。通过细胞实验验证发现,胃安散能通过调节TP53、AKT1、TNF和IL-6治疗胃癌。
    结论 胃安散活性成分可通过多途径、多靶点抑制胃癌进展,为后续研究提供了参考依据。

     

    Abstract: To explore the mechanism of action of Wei-An Powder in the treatment of gastric cancer based on network pharmacology and experimental verification.
    METHODS The active ingredients of Wei-An Powder were screened through databases such as TCMSP and TCM-ID to predict its target of action; potential targets for gastric cancer were screened through databases such as GeneCards and OMIM; after intersecting the target of the active ingredient with the potential target of gastric cancer, a protein-protein interaction (PPI) network was constructed using the String11. 0 database, and the PPI network was imported into Cytoscape 3.9.0 software to screen for core targets; GO functional and KEGG metabolic pathway enrichment analysis were performed using the DAVID database to predict the mechanism of action; molecular docking verification was carried out using Pyrx software. Using AGS gastric cancer cells, the analysis results of network pharmacology were validated through ELISA, qPCR, and Western blot experiments.
    RESULTS A total of 341 active ingredient targets and 7 031 potential targets for gastric cancer were identified through screening. After taking the intersection, a total of 743 targets for treating gastric cancer with Wei-An Powder were obtained, including core targets TP53, AKT1, TNF, and IL-6. GO and KEGG enrichment analysis showed that Wei-An Powder mainly exerted its effects through the cancer pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, and apoptosis pathway. The molecular docking results indicated that both the core target and the active ingredient had high binding activity. Through cell experiments, it was found that Wei-An Powder could treat gastric cancer by regulating TP53, AKT1, TNF, and IL-6.
    CONCLUSION The active ingredients of Wei-An Powder can inhibit the progression of gastric cancer through multiple pathways and targets, providing a reference for subsequent research.

     

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