基于网络药理学探讨阳和汤治疗三阴性乳腺癌的作用机制

Study on the mechanism of Yanghe Decoction in the treatment of triple negative breast cancer based on network pharmacology

目的通过网络药理学探讨阳和汤治疗三阴性乳腺癌的作用机制。方法通过TCMSP数据库筛选出阳和汤的药物主要活性成分及其靶点;通过GeneCards数据库筛选三阴性乳腺癌的潜在靶点;采用Cytoscape 3.7.2软件构建“药物-活性成分-靶基因-疾病”网络图;将整合后的阳和汤治疗三阴性乳腺癌的靶点导入STRING数据库构建蛋白质-蛋白质相互作用网络图,并通过R语言软件对关键靶点进行GO和KEGG富集分析。结果阳和汤治疗三阴性乳腺癌的主要活性成分有槲皮素、木樨草素、谷氨酸、油酸等。阳和汤的靶标基因与三阴性乳腺癌的靶标基因交集靶基因172个,如HIF-1α、EGFR、BCL2、VEGFA、IL-6、HK2等。GO功能富集分析得到GO条目2052个,KEGG通路富集分析得到信号通路154条通路,包括脂质和动脉粥样硬化通路、TNF信号通路、PI3K-Akt信号通路、HIF-1信号通路、IL-17信号通路、VEGF信号通路等。结论阳和汤治疗三阴性乳腺癌具有多成分、多通路、多靶点的特点,主要活性成分可能为槲皮素、木樨草素、谷氨酸、油酸,作用机制可能与调节细胞增殖、血管生成、免疫炎症反应、缺氧微环境、肿瘤代谢有关。

Objective To explore the mechanism of Yanghe Decoction in the treatment of triple negative breast cancer through network pharmacology.Methods The main active components and their targets of Yanghe Decoction were screened by TCMSP database;Potential targets of triple negative breast cancer were screened through GeneCards database;The network diagram of"drug active ingredient target gene disease"was constructed by using Cytoscape 3.7.2 software;The integrated targets of Yanghe Decoction for triple negative breast cancer were imported into STRING database to construct a network diagram of protein protein interaction,and GO and KEGG enrichment analysis of key targets was conducted through R language software.Results The main active ingredients of Yanghe Decoction in treating triple negative breast cancer were quercetin,luteolin,glutamic acid,oleic acid,etc.The target gene of Yanghe Decoction intersected with 172 target genes of triple negative breast cancer,such as HIF-1α,EGFR,BCL2,VEGFA,IL-6,HK2,etc.The GO function enrichment analysis obtained 2052 GO entries,and the KEGG pathway enrichment analysis obtained 154 signal pathways,including lipid and atherosclerosis pathway,TNF signal pathway,PI3K-Akt signal pathway,HIF-1 signal pathway,IL-17 signal pathway,VEGF signal pathway,etc.Conclusion Yanghe Decoction has the characteristics of multicomponent,multi-channel and multi-target in the treatment of triple negative breast cancer.The main active ingredients may be quercetin,luteolin,glutamic acid and oleic acid.The mechanism of action may be related to the regulation of cell proliferation,angiogenesis,immune inflammation,hypoxia microenvironment and tumor metabolism.