摘要
目的通过网络药理学联合分子对接技术探讨黄芪-莪术促进肺癌肿瘤血管正常化的潜在作用机制,为进一步研究寻找方向。方法利用公共数据库(TCMSP)检索并获取黄芪-莪术活性成分及相关靶点,通过基因卡、OMIM、TTD、药物GKB数据库和药物库数据,发现肺癌血管正常化的相关靶点,Met细胞景观插件ClueGO平台用于基因本体(GO)富集分析和京都基因组百科全书(KEGG)通路富集分析,最后利用AutoDock及Vina软件进行分子对接打分,Pymol软件进行对接结果的可视化展示。结果共筛选出486个黄芪-莪术生物活性成分和184个黄芪-莪术与肺癌肿瘤血管正常化相关的靶点;根据生物信息学分析,槲皮素、异鼠李素、山奈酚、7-O-甲基异脲醇、芒柄花黄素、毛芯异黄酮可能是黄芪-莪术调控肺癌肿瘤血管正常化的潜在活性成分,而RB1、MAPK1、EGFR、ESR1、AKT1、HIF1A、TP53、STAT1和CCND1是潜在的起效靶点;根据富集和分子对接结果显示异鼠李素与STAT1之间具有较高的结合亲和力,JAK2/STAT1通路可能是黄芪-莪术调控肺癌血管正常化的主要作用通路。结论黄芪-莪术促进肺癌肿瘤血管正常化作用的潜在机制可能是IFN-γ-JAK2/STAT1通路。
Objective To investigate the potential mechanism by which Radix Astragali Seu Hedysari-Rhizoma Curcumae promotes vascular normalization in lung cancer tumors via network pharmacology combined with molecular docking techniques.Methods The Genecards database(https://www.genecards.org),OMIM database(https://www.omim.org),TTD database(http://db.idrblab.net/ttd/),Drug GKB database(https://www.pharmgkb.org/),and Drugbank(https://go.drugbank.com/)were searched to identify targets related to vascular normalization in lung cancer while the public database(TCMSP)was search for active ingredients and related targets of Radix Astragali Seu Hedysari-Rhizoma Curcumae.Furthermore,Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genomes(KEGG)pathway enrichment analysis were performed using the Met Cell Landscape plugin ClueGO platform.Finally,molecular docking scoring was conducted using AutoDock and Vina software,and the docking results were visually presented using Pymol software.Results Based on the GO and KEGG enrichment combined with molecular docking results that showed a high binding affinity between isorhamnetin and STAT1,it was assumed that the JAK2/STAT1 pathway was the main pathway of action through which Radix Astragali Seu Hedysari-Rhizoma Curcumae regulated vascular normalization in lung cancer.Conclusion The potential mechanism by which vascular normalization of Radix Astragali Seu Hedysari-Rhizoma Curcumae promotes lung cancer tumors may be through the IFN-γ-JAK2/STAT1 pathway.
作者
于路航
于泓洋
田培裕
窦永起
YU Lu-hang;YU Hong-yang;TIAN Pei-yu;DOU Yong-qi(Medical School,General Hospital of Chinese PLA,Beijing 100853,China;The Sixth Medical Center,General Hospital of Chinese PLA,Beijing 100089,China)
出处
《解放军药学学报》
CAS
2024年第2期100-110,共11页
Pharmaceutical Journal of Chinese People's Liberation Army
基金
国家自然基金面上项目,No.82174118。
关键词
网络药理学
黄芪
莪术
肿瘤血管正常化
信号转导与转录激活因子1
network pharmacology
Radix Astragali Seu Hedysari
Rhizoma Curcumae
normalization of tumor vasculature
signal transducer and activator of transcription 1
