西黄丸治疗非小细胞肺癌作用机制的网络药理学探究和分子对接验证

王玥慧 王芬 李钰鑫 周杰 李志明 刘传波

摘要 目的：采用网络药理学和分子对接的方法探究西黄丸防治非小细胞肺癌（NSCLC）潜在分子机制。方法：在中药系统药理学数据库与分析平台（TCMSP）及BATMAN-TCM数据库中筛选分析西黄丸的有效活性成分及作用靶点。在GeneCards数据库与人类孟德尔遗传数据库（OMIM）中检索获取NSCLC的相关靶点，选取与西黄丸的交集靶点作为研究靶点。利用STRING数据库构建蛋白质-蛋白质相互作用（PPI）网络图。采用Cytoscape 3.7.0软件构建药物-靶点-疾病可视化互作网络图。使用DAVID数据对筛选分析出的关键靶点，进行基因本体（GO）功能富集分析和京都基因和基因组百科全书（KEGG）通路富集分析，最后运用AutoDock Vina软件和Pymol软件对药物有效活性成分和关键靶点进行分子对接验证。结果：通过筛选得到西黄丸51个主要活性成分，包括槲皮素、β-谷甾醇等，其中作用于NSCLC的靶点有178个，关键靶点有MAPK1、JUN、AKT1、TP53、RELA等。GO和KEGG分析结果显示，西黄丸治疗NSCLC的机制涉及多个生物学过程及PI3K-AKT信号通路、MAPK信号通路、TNF信号通路等多种信号通路。药物有效活性成分与关键靶点对接活性良好。结论：网络药理学分析显示西黄丸治疗NSCLC是多成分、多靶点、多通路协同起效，为后续相关实验提供了充分的理论依据。

关键词 西黄丸;非小细胞肺癌;网络药理学;分子对接;机制研究

Abstract To explore the potential molecular mechanism of Xihuang Pills in preventing and treating non-small cell lung cancer（NSCLC） by means of network pharmacology and molecular docking.Methods：The effective active components and targets of Xihuang Pills were screened and analyzed in TCM MSP and BATMAN-TCM database.We searched the related targets of NSCLC in GeneCards database and OMIM database，and selected the intersection target with Xihuang Pills as the research target.Protein-protein interaction network diagram was constructed by using STRING database.The network diagram of drug-target-disease visual interaction was constructed by using Cytoscape 3.7.0 software.GO function enrichment analysis and KEGG pathway enrichment analysis were carried out on the selected key targets by using DAVID data.Finally，the effective active ingredients and key targets of drugs were verified by molecular docking with AutoDock Vina software and Pymol software.Results：A total of 51 main active components of Xihuang Pills were screened，including quercetin，β-sitosterol，etc.Among them，there were 178 targets acting on NSCLC，and the key targets were MAPK1，JUN，AKT1，TP53，RELA，etc.GO and KEGG analysis showed that the mechanism of Xihuang Pills in treating NSCLC involved many biological processes and PI3K-Akt signal pathway，MAPK signal pathway，TNF signal pathway and other signal transduction pathways.The active ingredients of medicine had good docking activity with key targets.Conclusion：Network pharmacological analysis shows that Xihuang Pills is a multi-component，multi-target，multi-channel synergistic effect in the treatment of NSCLC，which provides sufficient theoretical basis for subsequent related experiments.

Keywords Xihuang Pills; NSCLC;Network pharmacology; Molecular docking; Mechanism research

中圖分类号：R285文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.24.001

肺癌是最常见的癌症，组织学类型中80%为非小细胞肺癌（Non-small Cell Lung Carcinoma，NSCLC）[1]，大部分患者就诊时已经处于中晚期，错过最佳治疗时期，预后极差。很多现代研究证明中医药能够有效减轻癌症患者的临床症状，提高生命质量，减少治疗带来的不良反应，更好地帮助NSCLC患者实现“带瘤生存”[2]。……