基于网络药理学探讨斑蝥素复方抗NSCLC的分子机制研究

Study on Molecular Mechanism of Compound Cantharidin against NSCLC Based on Network Pharmacology

摘要: 目的：基于网络药理学分析艾迪注射液抗NSCLC关键靶点和信号通路探讨其潜在的作用机制。方法：应用TCMSP数据库及TCMID数据库分别检索艾迪注射液中四味药物斑蝥、黄芪、人参、刺五加的化学成分及其对应的靶点，检索GEO数据库中NSCLC的潜在靶点，利用Perl将药物成分、成分靶点、疾病靶点等文件融合，通过PPI网络的拓扑结构分析能够发现其中的关键蛋白及其相互关系，利用clusterProfiler程辑包[100]进行GO及KEGG富集分析。结果：通过网络药理学分析，获取艾迪注射液的化学成分有51个，将化学成分靶点与疾病靶点取交集后得到81个艾迪治疗NSCLC的靶点，证明艾迪的抗肿瘤作用是通过多成分–多靶点的途径实现的。成分–靶点网路图的拓扑分析显示槲皮素、山柰酚、7-O-甲基异微凸剑叶莎醇、异鼠李素、豆甾醇等度值较高，可能为艾迪有效成分中的关键药效物质，靶点方面PTGS2、ADRB2、ALOX5等度值较高，可能作为艾迪抗NSCLC的重要靶点。结论：本研究初步探明了艾迪注射液抗NSCLC的化学成分、靶点通路及相互作用关系。艾迪中抗NSCLC的关键成分为槲皮素、山柰酚、异鼠李素、豆甾醇等，主要是通过抗氧化、抑制EMT、调节金属离子及类固醇激素应答、促进肿瘤细胞凋亡等方式来发挥抗癌作用。

Abstract: Objective: To analyze the key targets and signaling pathways of Aidi injection against NSCLC based on network pharmacology to explore its potential mechanism of action. Methods: The TCMSP database and TCMID database were used to search the chemical constituents and their corresponding targets of the four drugs Zanthoxylum, Astragalus, Ginseng and Acanthopanax in Aidi injection, and to search the potential targets of NSCLC in the GEO database, and the files of drug constituents, constituent targets and disease targets were fused by using Perl, and the key protein and their interrelationships could be found through the topology analysis of the PPI network. Key proteins and their interrelationships were identified by topological analysis of the PPI network, and GO and KEGG enrichment analyses were carried out using the cluster Profiler program package [100]. Results: Through the network pharmacology analysis, 51 chemical components of Aidi injection were obtained, and 81 targets of Aidi for NSCLC were obtained after taking the intersection of chemical component targets and disease targets, which proved that the antitumor effect of Aidi was realized through the multi-component-multi-target pathway. The topological analysis of the component-target network diagram showed that quercetin, kaempferol, 7-O-methylisocamptothecin, isorhamnetin, and stigmasterol had higher degree values, which might be the key pharmacodynamic substances in the active ingredients of Aidi, and the targets of PTGS2, ADRB2, and ALOX5 had higher degree values, which might be the important targets of Aidi for the anti-NSCLC. Conclusion: This study preliminarily investigated the chemical composition, target pathway and interaction relationship of anti-NSCLC in Aidi injection. The key anti-NSCLC components in Aidi are quercetin, kaempferol, isorhamnetin, and stigmasterol, which mainly exert their anticancer effects through antioxidant, EMT inhibition, modulation of metal ions and steroid hormone response, and promotion of tumor cell apoptosis.