黄芪治疗乳腺癌机制研究

Molecular Mechanism of Astragalus mongholicus in the Treatment of Breast Cancer

基于网络药理学理论,采用生物信息学手段对中药黄芪中治疗乳腺癌有效成分及其机制进行探讨.一方面通过TCMSP中草药系统药理学平台筛选出黄芪的有效成分,另一方面通过GeneCards、OMIM、PharmGkb、TTD、DrugBank和DisGeNET等数据库查找与乳腺癌相关靶点.而后,利用筛选出的有效成分和靶点构建"药物-成分-靶点-疾病"网络图,借助STRING数据库平台探究蛋白质互相作用关系,并进行GO分析和KEGG通路富集分析.采用分子对接技术将黄芪中的主要活性成分槲皮素与JUN、RELA、ESR1、MYC、MAPK1、FOS、HIF1A、MAPK14、AKT1、CCND1和IL-2等靶点进行分子对接.最后进行槲皮素(quercetin)对人乳腺癌MCF-7和MDA-MB-435细胞模型进行体外实验验证,结果表明黄芪可能主要是通过其活性成分槲皮素实现其抗乳腺癌的作用.本研究初步探讨黄芪治疗乳腺癌具有的多靶点、多通路的潜在作用机制,可进一步为黄芪抗乳腺癌有效成分的筛选验证提供依据.

Based on network pharmacology and molecular docking technology, the mechanism of Astragalus mongholicus in the treatment of breast cancer was discussed. The effective components of Astragalus mongholicus were screened through the traditional Chinese Medicine System Pharmacology database(TCMSP), and the targets related to breast cancer were found through GeneCards, OMIM, PharmGkb,TTD, DrugBank, and DisGeNET databases. STRING database was used for the protein-protein interaction(PPI)network analysis, and Cytoscape software was used to construct a network diagram of "drug-component-target-disease. R software was used to analyze the Gene Ontology(GO)molecular function and genomes(KEGG)signaling pathway enrichment of the core targets. Molecular docking technology was used to dock quercetin with RELA,AKT1,CCD1,FOS,ESR1,IL-2,JUN,MYC,MAPK1,MAPK14, and HIF1A.Finally, the cell counting kit-8(CCK 8) method was used to determine the effect of quercetin on the proliferation of breast cancer MCF-7 and MDA-MB-435 cells, and the results showed that Astragalus mongholicus had a more substantial inhibitory effect on breast cancer MCF-7 and MDA-MB-435 cells through its active ingredient quercetin. This study preliminarily explored the potential mechanism of Astragalus mongholicus with targets and pathways in the treatment of breast cancer. It provided a basis for subsequent verification of the molecular mechanism of Astragalus mongholicus against breast cancer.