基于网络药理学探讨槐耳治疗肺癌的作用机制

To Investigate the Mechanism of Action of Huaier Granule in Treating Lung Cancer Based on Network Pharmacology

摘要

目的：应用网络药理学研究槐耳治疗肺癌的有效成分及其可能作用机制。方法：应用 SwissADME 和 Swiss Target Prediction 数据库筛选槐耳有效成分和药物靶点，通过 GeneCards、OMIM、TTD、PharmGkb 和 DrugBank 数据库筛选肺癌的靶点；将槐耳有效成分的药物靶点与疾病靶点取交集，所得交集靶点导入 String 数据库构建 PPI 网络，利用 Metascape 数据库进行 GO 和 KEGG 富集分析；利用 Cytoscape 软件构建槐耳 - 成分 - 靶点 - 通路网络，并分析槐耳治疗肺癌作用的功能和作用通路；最后运用 AutoDock 软件对活性成分和核心靶点进行分子对接验证。结果：槐耳潜在有效活性成分 18 个，肺癌靶点 1 632 个，槐耳与肺癌的交集靶点共有 151 个，经过分析筛选出槐耳治疗肺癌的关键靶点为 10 个。GO 和 KEGG 分析结果显示交集靶点主要富集于激素的反应、细胞对脂质的反应、磷代谢过程的正向调节、细胞周期蛋白依赖性蛋白激酶全酶复合物、膜筏、蛋白激酶活性、激酶结合和癌症通路、癌症中 MicroRNAs、癌症中的转录失调等。分子对接结果显示槐耳重要成分与核心靶点 MMP9 有最佳的结合能。结论：通过网络药理学研究显示，槐耳治疗肺癌的作用机制主要体现在调控细胞增殖、蛋白激酶活性和调节激素等方面。

Abstract

Objective: To study the effective components and possible mechanisms of action of Huaier in the treatment of lung cancer by applying network pharmacology. Methods: The effective components and drug targets of Huaier were screened by using the SwissADME and Swiss Target Prediction databases, and the targets of lung cancer were screened by using the GeneCards, OMIM, TTD, PharmGkb and DrugBank databases. The drug targets and disease targets of the effective components of Huaier were taken as intersections. The obtained intersection targets were imported into the String database to construct the PPI network, and GO and KEGG enrichment analyses were conducted using the Metascape database. The Cytoscape software was used to construct the network of Huaier - components - targets - pathways. Finally, the AutoDock software was used to verify the molecular docking of the active ingredients and the core targets. Results: The results showed that there were 18 potential active ingredients, 1 632 targets of lung cancer, 151 intersection targets of Sophora L. and lung cancer, and 10 key targets of Huaier for the treatment of lung cancer were selected through analysis. The results of GO and KEGG analyses indicated that the intersection targets were mainly enriched in hormone responses, positive regulation of phosphorus metabolism processes, protein kinase activity, kinase binding and cancer pathways, and transcriptional dysregulation in cancer, etc. The molecular docking results showed that the important components of Huaier had the best binding energy with the core target MMP9. Conclusion: From the aspect of network pharmacology, the mechanism of action of Huaier in the treatment of lung cancer is mainly reflected in the regulation of cell proliferation, protein kinase activity and hormone regulation.

关键词

槐耳 / 肺癌 / 网络药理学 / 靶点 / 信号通路

Key words

huaier / lung cancer / network pharmacology / target / signaling pathway

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基金资助

河北省中医药管理局科研计划项目(2022146)

张家口市重点研发计划项目(2221108D)