基于网络药理学与生物信息学探究华蟾酥毒基治疗胃癌的作用机制

doi:10.16098/j.issn.0529-1356.2025.01.006

摘要/Abstract

摘要：

目的基于网络药理学结合生物信息学、分子对接技术，探究华蟾酥毒基（cinobufagin，CBG）治疗胃癌的作用机制。方法利用PubChem 数据库、TCMSP 数据库和SwissTargetPrediction数据库，收集CBG治疗胃癌活性成分的结构及其潜在靶点。从TGGA数据库获取胃癌样本转录组数据，通过差异基因分析获取胃癌相关靶点。取CBG靶点和胃癌疾病靶点的交集，进行基因本体论（GO）和京都基因和基因组百科全书（KEGG）富集分析。使用 STRING 数据库对共同靶点构建蛋白蛋白相互作用(PPI) 网络，通过Cytoscape 软件筛选核心靶点，SYBYL-X 2.1.1 软件将筛选得到的核心靶点和CBG进行分子对接，进一步筛选出得分排名前10的靶点，利用Kaplan-Meier plotter数据库筛选出与胃癌患者生存期密切相关的靶点。结果CBG治疗胃癌涉及59个靶点，关键核心靶点19个，其中关键靶点极光激酶 A （AURKA）、肝细胞生长因子受体细胞周期蛋白依赖性激酶1（CDK1）、增强子同源物2（EZH2）、肝细胞生长因子受体（MET）、基质金属蛋白酶3（MMP-3）、孕酮受体（PGR）、前列腺素内过氧化物合酶1（PTGS1）和胸苷酸合成酶（TYMS）与CBG具有较好的结合活性，且与胃癌预后密切相关。结论CBG可能通过多靶点、多途径来发挥抗胃癌作用。

关键词:

华蟾酥毒基, 胃癌, TCGA数据库, 网络药理学, 分子对接

Abstract:

Objective To explore the mechanism of cinobufagin (CBG) in treating gastric cancer based on network pharmacology combined with bioinformatics and molecular docking technology. Methods Active ingredients and potential targets of CBG in treating gastric cancer were collected from PubChem, TCMSP, and SwissTargetPrediction databases. Transcriptional data of gastric cancer samples were obtained from TGGA database, and gastric cancer-related targets were identified through differential gene analysis. Intersection of targets between CBG and gastric cancer diseases was subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Protein-protein interaction (PPI) network of common targets was constructed using STRING database, and core targets were selected using Cytoscape software. Molecular docking verification of core targets screened with SYBYL-X 2.1.1 software was conducted with CBG. Results CBG treatment of gastric cancer involved 59 targets, with 19 key targets identified. Key targets such as aurora kinase A(AURKA), cyclin-dependent kinase 1(CDK1), enhancer of zeste homolog 2(EZH2), hepatocyte growth factor receptor (MET), matrix metallopeptidase 3(MMP-3), progesterone receptor (PGR), prostaglandin-endoperoxide synthase 1(PTGS1), and thymidylate synthase (TYMS) which exhibited good binding activity with CBG and were closely associated with gastric cancer prognosis. Conclusion CBG may exert anti-gastric cancer effects through multiple targets and pathways.

Key words: Cinobufagin, Gastric cancer, TCGA database, Network pharmacology, Molecular docking

中图分类号:

R741
R392

张昊李雪岩李玲敏简白羽. 基于网络药理学与生物信息学探究华蟾酥毒基治疗胃癌的作用机制[J]. 解剖学报, 2025, 56(1): 43-49.

ZHANG Hao LI Xue-yan LI Ling-min JIAN Bai-yu. Investigating mechanism of cinobufagin in gastric cancer treatment based on network pharmacology and bioinformatics[J]. Acta Anatomica Sinica, 2025, 56(1): 43-49.

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