康艾注射液干预乳腺癌的网络药理学研究

Network Pharmacological Study on the Intervention of Kang’ai Injection in Breast Cancer

目的基于网络药理学探讨康艾注射液治疗乳腺癌的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)和SwissTargetPrediction数据库获取康艾注射液中药活性成分及靶点,并利用UniProt数据库规范靶点基因名称;借助GeneCards、OMIM数据库筛选乳腺癌疾病靶点,通过STRING数据库及Cytoscape3.6.1软件构建蛋白相互作用网络。借助Metascape软件平台对交集靶点进行GO功能与KEGG通路富集分析,并对有效活性成分及疾病靶点进行分子对接初步验证。结果共筛选出康艾注射液治疗乳腺癌的潜在活性成分21种,关键靶点5个,富集分析得到重要生物过程、细胞成分、分子功能各10项及20条相关通路。其中,康艾注射液主要通过参与膜筏、细胞外基质、转录因子复合体等生物反应,作用于肿瘤坏死因子、铂类药物耐药、MAPK、FOXO、JAK-STAT及雌激素信号通路等发挥抗癌作用。结论康艾注射液治疗乳腺癌的关键活性成分是氧化苦参碱、槲皮素、山柰酚,其作用机制主要与MAPK信号通路密切相关。

Objective To explore the mechanism of Kang’ai Injection in the treatment of breast cancer based on network pharmacology.Methods The effective components and targets of Kang’ai Injection were obtained through the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)and SwissTargetPrediction database,and the UniProt database was used to standardize the target gene names;the GeneCards and OMIM databases were used to screen predicted targets of breast cancer disease,and STRING database and Cytoscape 3.6.1 software were used to construct a protein-protein interaction network.With the help of Metascape software platform,GO function enrichment and KEGG pathway enrichment analysis of the intersection targets were carried out,and the effective active components and disease targets were initially verified by molecular docking.Results A total of 21 potential active components and 5 key targets of Kang’ai Injection in the treatment of breast cancer were screened out.The enrichment analysis revealed 10 items of important biological process,cellular component,molecular function,and 20 related pathways.Among them,Kang’ai Injection mainly participated in biological reactions such as membrane rafts,extracellular matrix,and transcription factor complexes,acted on tumor necrosis factor,platinum drug resistance,MAPK,FOXO,JAKSTAT and estrogen signaling pathways,in order to achieve anti-cancer effect.Conclusion The key components of Kang’ai Injection in the treatment of breast cancer are oxymatrine,quercetin,and kaempferol.The mechanism of action is mainly related to the MAPK signaling pathway.