基于网络药理学和分子对接技术探讨扶正抑瘤方治疗肺鳞癌的作用机制

Exploring the Mechanism of Fuzheng Anti-Tumor Prescription in the Treatment of Lung Squamous Cell Carcinoma Based on Network Pharmacology and Molecular Docking Technology

摘要: 目的：运用在线数据库研究扶正抑瘤方治疗肺鳞癌的潜在作用机制，为进一步实验验证提供理论基础。方法：通过中药系统药理学数据库与分析平台(TCMSP)收集扶正抑瘤方中四味中药的主要有效成分，通过Genecards数据库收集肺鳞癌的疾病靶点，将中药有效成分靶点与肺鳞癌疾病靶点取交集，并通过Cytoscape3.8.0软件绘制中药–有效成分–疾病–靶点网络图；利用String数据库获取蛋白相互作用网络；通过DAVID数据库对交集靶点进行GO功能富集和KEGG通路富集。利用Pubchem数据库、Uniprot数据库、PDB数据库和AutoDock Tools 1.5.6软件、AutoDock Vina 1.1.2进行分子对接，使用Pymol软件可视化分子对接结果。结果：收集到扶正抑瘤方有效成分19个，基因靶点194个，肺鳞癌疾病靶点6447个，二者相交集靶点170个，主要靶点有NOS2、PTGS1、CHRM3、ESR1、SCN5A、PTGS2、RXRA等。GO功能富集得到生物过程条目2203个、细胞成分条目58个、分子功能条目169个；KEGG通路富集共计170条信号通路；主要涉及流体剪切应力和动脉粥样硬化通路等。结论：本研究采用网络药理学的方法揭示了扶正抑瘤方在肺鳞癌治疗中多成分、多靶点、多途径的特点，通过可视化的分子对接结果显示有效成分来自扶正抑瘤方与靶点的特异性结合位点，其中JUN、AKT1可能为主要作用靶点。本研究为进一步研究扶正抑瘤方治疗肺鳞癌的药理机制提供基础，为后续的实验验证和临床应用提供了理论依据。

Abstract: Objective: To investigate the potential mechanism of Fuzheng anti-tumor prescription in the treat-ment of lung squamous cell carcinoma by using online database, and to provide theoretical basis for further experimental verification. Methods: The main active components of four herbs in Fuzheng anti-tumor prescription were collected by the Systematic Pharmacology database and Analysis Platform (TCMSP). The disease targets of lung squamous cell carcinoma were collected by Genecards database. The targets of the active components of traditional Chinese medicine and lung squamous cell carcinoma were taken as the intersection. Cytoscape3.8.0 software was used to draw network map of drugs-active ingredients-disease-target; The protein interaction network was obtained using String database. GO function enrichment and KEGG pathway enrichment were performed on the in-tersection target through DAVID database. Pubchem database, Uniprot database, PDB database, AutoDock Tools 1.5.6 software and AutoDock Vina 1.1.2 software were used for molecular docking, and Pymol software was used to visualize molecular docking results. Results: 19 active components, 194 gene targets and 6447 lung squamous cell carcinoma disease targets of the prescription were collected, and 170 intersecting targets were collected, including NOS2, PTGS1, CHRM3, ESR1, SCN5A, PTGS2, RXRA, etc. GO function enrichment obtained 2203 biological process items, 58 cell compo-nent items and 169 molecular function items. A total of 170 signaling pathways were enriched through KEGG pathway. It mainly involves fluid shear stress and atherosclerotic pathways; Hepati-tis C pathway, etc. Conclusion: This study adopts the network pharmacology method reveals the centralizer tumor suppression in the treatment of lung squamous carcinoma, multiple components, multiple targets, multiple ways of characteristics, among them, JUN, AKT1 as the main targets for treatment of lung squamous carcinoma, by visualizing the molecular docking results show effective components from the centralizer tumor suppression party and target specific binding sites. This study provided a basis for further study of the pharmacological mechanism of Fuzheng anti-tumor prescription in the treatment of lung squamous cell carcinoma, and provided a theoretical basis for subsequent experimental verification and clinical application.