基于网络药理学探讨黄芪对胰腺癌的作用机制

MECHANISM OF ACTION OF ASTRAGALUS MEMBRANACEUS IN TREATMENT OF PANCREATIC CANCER:AN ANALYSIS BASED ON NETWORK PHARMACOLOGY

目的 运用网络药理学,探讨黄芪抗胰腺癌的主要活性成分及作用靶点,并预测作用机制及对免疫微环境的影响。方法 通过TCMSP数据库筛选黄芪的主要活性成分,并通过GeneCards和OMIM数据库收集胰腺癌疾病靶点,利用Cytoscape软件构建疾病-药物-靶点网络图。通过String数据库绘制蛋白相互作用网络并筛选出核心靶点,通过Human Protein Atlas和PROGgeneV2数据库对核心靶点进行蛋白表达及TCGA生存分析,进一步通过TIMER数据库分析核心靶点与肿瘤免疫细胞浸润的关系。最后利用Metascape、Bioconductor平台和R语言进行GO分子功能分析和KEGG通路分析。结果 筛选共得到黄芪20种活性成分,作用于胰腺癌56个靶点。在胰腺癌中,核心靶点Caspase3和MYC高表达组患者预后明显差于低表达组(P<0.05),同时,Caspase3和MYC会影响肿瘤免疫细胞在胰腺癌中的浸润情况。分子功能和通路分析结果表明黄芪作用的靶点主要与癌症的调控、细胞凋亡、对类固醇激素的反应、对无机物和有机物的反应等生物过程相关,黄芪通过调节PI3K-AKT、Erb、MAPK等通路来影响胰腺癌的发展。结论 黄芪对胰腺癌的治疗作用体现了中药多组分、多靶点的特点,为进一步探究其抗胰腺癌的作用机制提供了依据。

Objective To investigate the main active components and targets of Astragalus membranaceus in the treatment of pancreatic cancer based on network pharmacology,and to predict its mechanism of action and influence on immune mic-roenvironment.Methods The Traditional Chinese Medicine Systems Pharmacology database was used to screen out the main active components of Astragalus membranaceus,GeneCards and OMIM databases were used to collect the targets of pancreatic can-cer,and Cytoscape software was used to establish the disease-drug-target network.The String database was used to plot protein-protein interaction network and screen out core targets,the Human Protein Atlas and PROGgeneV2 databases were used to perform protein expression and TCGA survival analyses of the core targets,and then the TIMER database was used to analyze the association between core targets and tumor immune cell infiltration.The Metascape and Bioconductor platforms and the R language were used to perform gene ontology(GO)molecular function analysis and KEGG pathway analysis.Results A total of 20 active components of Astragalus membranaceus were screened out,which acted on 56 targets of pancreatic cancer.As for the patients with pancreatic cancer,the patients with high expression of the core targets caspase-3 and MYC had a significantly poorer prognosis than those with low expression(P<0.05),and in addition,caspase-3 and MYC affected tumor immune cell infiltration in pan-creatic cancer.The molecular function and pathway analyses showed that Astragalus membranaceus acted on the targets involved in the biological processes such as cancer regulation,cell apoptosis,response to steroid hormone,and response to inorganic and organic substances,and Astragalus membranaceus affected the progression of pancreatic cancer by regulating the PI3K-AKT,Erb,and MAPK pathways.Conclusion Various components and targets are involved in the treatment of pancreatic cancer by Astra-galus membranaceus,which provides a basis for further research on its mechanism of action in the treatment of pancreatic cancer.