基于网络药理学和分子对接技术探究盐地碱蓬抗乳腺癌的机制

Systematic elucidation of the pharmacological mechanisms of Suaeda salsa for treating breast cancer via network pharmacology

目的应用网络药理学方法和分子对接技术探讨盐地碱蓬的活性成分对于乳腺癌辅助治疗的潜在机制。方法通过文献研究结合中药系统药理学数据库和分析平台(traditional chinese medicine systems pharmacology,TCMSP)筛选出盐地碱蓬的主要药效成分,通过SwissTargetPrediction数据库对药效成分的靶标进行预测。同时,通过查询GeneCards网站和DisGeNet数据库得到乳腺癌的相关靶点。将药物和疾病的靶点进行匹配,得到共同靶点列表,之后将列表导入STRING在线分析平台,构建分子靶点蛋白之间的互作网络,利用cytoscape3.8.0软件进行可视化并筛选核心靶点。通过R软件进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)分析,运用AutoDock Vina和Pymol将有效成分与核心靶标进行分子对接。结果盐地碱蓬主要的药效成分有3种,与乳腺癌相关的靶点有179个。GO分析显示靶点主要集中在上皮细胞增殖的调控、氧化应激反应、ERK1和ERK2下游信号通路等。KEGG分析得到富集通路主要是与肿瘤发生发展相关的通路,如MAPK信号通路、内分泌抵抗信号通路、乳腺癌信号通路等。分子对接显示3种活性成分与关键靶点具有较好结和力。结论盐地碱蓬的主要活性成分可能通过多靶点调节多条信号通路辅助干预乳腺癌。本研究可为后期抗肿瘤药物开发提供参考。

Objective To uncover the potential effective components and mechanism of Suaeda salsa in the treatment of breast cancer based on network pharmacology.Methods The effective components of Suaeda salsa were retrieved from other articles and screened by tcmsp.The corresponding targets of the effective components were collected from the SwissTargetPrediction website.Targets of breast cancer were collected from GeneCards and DisGeNet databases.The intersection of Suaeda salsa target genes and breast cancer target genes was performed using the“VennDiagram”package in R software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the targets were performed via R software.Cytoscape software was used to construct a compound network.A protein-protein interaction(PPI)network was generated by using the STRING database.Key targets were filtered by utilizing the CytoNCA plugin.Molecular docking analysis was used to check the affinity of active ingredients to the central targets.Results The results revealed that there were 3 active compounds of Suaeda salsa which have 179 targets associated with breast cancer.GO analysis suggested that these targets were significantly enriched in factors associated with regulation of epithelial cell proliferation,oxidative stress and ERK1 and ERK2 cascade,etc.KEGG pathways mainly involved cancer-related pathways such as the MAPK signaling pathway and endocrine resistance and breast cancer.The results of molecular docking showed that the active compounds had a high affinity with the core targets.Conclusion The present study demonstrates that Suaeda salsa exerts therapeutic effects in breast cancer through multiple targets and pathways and provides evidence to support its potential development as a promising Chinese medicine.