中国比较医学杂志2026，Vol.36Issue(14)：48-63,16.DOI:10.3969/j.issn.1671-7856.2026.14.005
基于网络药理学和实验验证探究黄芪治疗肺腺癌的作用机制
Exploring the mechanisms involved in Astragalus membranaceus treatment of lung adenocarcinoma through network pharmacology and experimental validation
摘要
Abstract
Objective To elucidate the therapeutic mechanism of Astragalus membranaceus in lung adenocarcinoma(LUAD)through network pharmacology,molecular docking,and in vitro validation.Methods A.membranaceus active components were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Integrative Pharmacology-based Network Computational Research Platform of Traditional Chinese Medicine(TCMIP)databases as well as literature,and their potential targets were predicted using SwissTargetPrediction.LUAD-related targets were obtained from GEO,OMIM,DisGeNET,and GeneCards databases.A protein-protein interaction network was constructed using the STRING database.A synergistic network of core components and their co-regulated target clusters was constructed to explore the multi-target regulatory mechanism involved.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify key biological processes and signaling pathways.Protein expression differences of core targets in LUAD tissues were validated using the Human Protein Atlas(HPA)database,and molecular docking between key targets and major active components was assessed using AutoDock.The effects of core components on LUAD cell proliferation,migration,apoptosis,and core target mRNA expression were evaluated using MTT,colony formation,wound healing,flow cytometry,and RT-qPCR.Results 44 active components(including quercetin,(R)-isomucronulatol,and kaempferol)and 58 corresponding potential targets were identified;core targets included TP53,AKT1,IL6,EGFR,CASP3,TNF,and BCL2.Enrichment analyses suggested that A.membranaceus may exert anti-LUAD effects by modulating biological processes such as oxidative stress,lipopolysaccharide response,response to bacterial-derived molecules,and chemical stress responses,primarily through PI3K-AKT,lipid and atherosclerosis,and MAPK signaling.HPA database validation revealed that TP53,AKT1,EGFR,CASP3,and BCL2 protein expression was upregulated in LUAD tissues.Molecular docking confirmed strong binding affinities between core components and their respective targets.In vitro experiments demonstrated that quercetin,(R)-isomucronulatol,and kaempferol(50 μg/mL)significantly inhibited LUAD cell proliferation and migration,and induced apoptosis(P<0.05).These compounds upregulated tumor suppressor gene mRNA expression(TP53,CASP3,and downregulated oncogenes(AKT1,IL6,EGFR,and BCL2)(P<0.05).Conclusions A.membranaceus exhibited therapeutic potential against LUAD through a multi-target,multi-pathway mechanism,involving PI3K-AKT,lipid and atherosclerosis,and MAPK signaling.关键词
黄芪/肺腺癌/网络药理学/分子对接/PI3K-AKT信号通路Key words
Astragalus membranaceus/lung adenocarcinoma/network pharmacology/molecular docking/PI3K-AKT signaling pathway分类
医药卫生引用本文复制引用
袁雨萱,王纯,袁瑞娇,李琪,李克娟..基于网络药理学和实验验证探究黄芪治疗肺腺癌的作用机制[J].中国比较医学杂志,2026,36(14):48-63,16.基金项目
四川省自然科学基金项目(22NSFSC1568). （22NSFSC1568）
