基于网络药理学和分子对接预测泮托拉唑治疗肺癌的靶点与分子机制
Prediction of the target and molecular mechanism of pantoprazole therapy for lung cancer based on network pharmacology and molecular docking
吴晓婷 1王剑 1李婷艳1
作者信息
- 1. 杭州市临平区第一人民医院 呼吸与危重症医学科,浙江 杭州 311100
- 折叠
摘要
目的 运用网络药理学、分子对接方法探索泮托拉唑治疗肺癌的关键靶点及分子作用机制.方法 通过Swiss TargetPrediction数据库预测泮托拉唑治疗肺癌的作用靶点,采用GeneCards、OMIM等数据库搜索肺癌的相关靶点,取 2 者的交集靶点获得潜在靶点;应用STRING数据库找出靶点的作用关系,使用 Cytoscape3.10.0 软件构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络并筛选核心靶点.利用DAVID网站进行基因本体(gene ontology,GO)功能及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,利用AutoDock 软件进行分子对接.结果 获得 105 个泮托拉唑的作用靶点、2 180 个肺癌相关靶点,两者取交集后共得到 41 个泮托拉唑治疗肺癌的作用靶点.在PPI网络中,EGFR、ERBB2、PIK3CA、MMP9 等13 个靶点处于核心位置.GO 富集分析和 KEGG 通路分析显示,泮托拉唑调控的核心靶点与细胞信号通路激活、肿瘤进展、肿瘤耐药等机制密切相关;分子对接结果显示,泮托拉唑与核心靶点均有较强的相互作用.结论 泮托拉唑可能通过EGFR、ERBB2、PIK3CA、MMP9 等靶点及多条信号通路治疗肺癌.
Abstract
Objective To explore the key targets and molecular mechanisms of pantoprazole in the treatment of lung cancer by using network pharmacology and molecular docking methods.Methods The target of pantoprazole was predicted by Swiss TargetPrediction database;GeneCards,OMIM and other databases were employed to search the relevant targets of lung cancer.The intersection of pantoprazole's action target and lung cancer target was used to obtain potential targets.The STRING database was applied to elucidate the relationships among the targets,and Cytoscape 3.10.0 software was used to construct a protein-protein interaction(PPI)network and to select core targets.The DAVID website was employed for gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.Molecular docking was performed using the AutoDock software.Results A total of 105 target proteins for pantoprazole and 2,180 lung cancer-related targets were identified.After taking the intersection,41 target proteins were identified as potential targets for pantoprazole in treating lung cancer.In the PPI network,13 targets including EGFR,ERBB2,PIK3CA,and MMP9 were identified as core targets.GO enrichment analysis and KEGG pathway analysis revealed that the core targets regulated by pantoprazole were closely associated with cell signaling pathway activation,tumor progression,and drug resistance mechanisms.Molecular docking results indicated strong interactions between pantoprazole and the core targets.Conclusions Pantoprazole may potentially treat lung cancer through targeting proteins such as EGFR,ERBB2,PIK3CA,and MMP9,as well as through multiple signaling pathways.
关键词
泮托拉唑/肺癌/网络药理学/分子对接Key words
pantoprazole/lung cancer/network pharmacology/molecular docking引用本文复制引用
基金项目
浙江省基础公益研究项目(LGF19H010002)
浙江省医药卫生科技计划创新引导专项(2023XY010)
出版年
2024
国家科技期刊平台
NSTL
万方数据