【摘要】 目的 基于生信分析、网络药理学及分子对接等探索陈氏散结汤抗胰腺癌作用机制。方法 通过中药系统药理学数据库与分析平台、HERB和UniProt数据库获取陈氏散结汤活性成分和作用靶点，通过GeneCards和OMIM数据库获取胰腺癌疾病靶点，通过GEO数据库筛选胰腺癌特征基因。利用EVenn工具筛选共同作用靶点，基于STRING 11.5数据库构建蛋白质-蛋白质相互作用网络，通过Cytoscape 3.9.1建立“中药-活性成分-交集靶点”网络可视化。使用DAVID数据平台进行基因本体和京都基因和基因组数据库富集分析，并使用AutoDockVina 1.1.2和PyMol V2.6.2教育版进行分子对接及可视化处理。结合TCGA数据库中胰腺癌患者数据，分析核心靶蛋白表达水平与临床病理特征及预后的关系。结果 共筛选出陈氏散结汤活性成分106个（如木犀草素、槲皮素、柚皮素等），作用靶点749个，胰腺癌疾病靶点1 341个，胰腺癌特征基因398个，“陈氏散结汤活性成分-胰腺癌”共同潜在治疗靶点166个（如MET、ESR2、NOS2等），其中胰腺癌特征基因有11个。主要作用于PI3K-Akt、EGFR-TKIs耐药等信号通路。分子对接发现核心活性成分与核心靶点对接活性良好，木犀草素与MET的结合能最低。MET为胰腺癌特征基因，高表达MET患者年龄更小、组织学分级更高且总生存期更短。结论 陈氏散结汤关键活性成分木犀草素、槲皮素、柚皮素主要作用于MET、ESR2、NOS2等靶点发挥抗胰腺癌作用，MET可能为其主要靶点。更多还原

【Abstract】 Objective To explore the mechanism of Chen’s Sanjie Decoction against pancreatic cancer via bioinformatics, network pharmacology, and molecular docking. Methods Active components and action targets of Chen’s Sanjie Decoction were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, HERB, and UniProt databases. Pancreatic cancerrelated targets were obtained from GeneCards and OMIM databases, while characteristic genes of pancreatic cancer were screened from GEO databases. The EVenn tool was used to screen for common interaction targets. A proteinprotein interaction network was constructed based on the STRING 11.5 database, and the “traditional Chinese medicine-active components-intersection targets” network visualization was established using Cytoscape 3.9.1. The DAVID data platform was used for gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Molecular docking and visualization processing were conducted using AutoDockVina 1.1.2 and PyMol V2.6.2 educational version. Based on the data of pancreatic cancer patients in the TCGA database, the relationship between the expression levels of core target proteins and clinical pathological characteristics as well as prognosis was analyzed. Results A total of 106 active components of Chen’s Sanjie Decoction were identified(such as luteolin, quercetin, naringenin, etc.), a total of 749 action targets were discovered, 1 341 disease targets related to pancreatic cancer were identified, and 398 characteristic genes of pancreatic cancer were found. The “active ingredients of Chen’s Sanjie Decoction-pancreatic cancer” had 166 common potential therapeutic targets(such as MET, ESR2, NOS2, etc.), among which there were 11 characteristic genes for pancreatic cancer. It mainly acted on the PI3K-Akt, EGFR-TKIs resistance and other signaling pathways. Molecular docking analysis revealed that the core active component had good binding activity with the core target, and luteolin had the lowest binding energy with MET. MET was a characteristic gene for pancreatic cancer. Patients with high expression of MET were younger, had a higher histological grade, and had a shorter overall survival period. Conclusion Key components of Chen’s Sanjie Decoction, including luteolin, quercetin, and naringenin, exert antipancreatic cancer effects primarily via targets such as MET, ESR2, and NOS2, with MET as a potential central target.更多还原