引用本文:宋思源1,2,3,舒鹏1,2,3.基于网络药理学及体外实验验证研究茯苓-白术药对治疗胃癌的作用机制[J].世界中医药,2022,(20):. |
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基于网络药理学及体外实验验证研究茯苓-白术药对治疗胃癌的作用机制 |
Mechanism of Poria-atractylodis Macrocephalae Rhizoma Drug Pair in the Treatment of Gastric Cancer Based on Network Pharmacology and In Vitro Experimental Verification |
投稿时间:2020-11-04 |
DOI:10.3969/j.issn.1673-7202.2022.20.002 |
中文关键词: 茯苓 白术 网络药理学 胃癌 富集分析 作用机制 核心靶点 |
English Keywords:Poria Atractylodis Macrocephalae Rhizoma Network pharmacology Gastric Cancer Enrichment analysis Mechanism Core targets |
基金项目:国家自然科学基金面上项目(81673918);国家中医药管理局中医药循证能力建设项目(2019XZZX-ZL003);南京中医药大学中医学优势学科三期项目开放课题(ZYX03KF020);江苏省中医药管理局科技项目(ZD201803) |
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中文摘要: |
目的:基于网络药理学及实验验证,探讨茯苓-白术药对治疗胃癌的作用机制。方法:根据口服生物利用度和类药性,在中药系统药理学数据库与分析平台(TCMSP)筛选茯苓-白术药对活性成分,借助Swiss Target Prediction数据库,预测茯苓-白术药对活性成分的潜在靶点。在疾病相关基因数据库(DisGeNET)检索胃癌相关靶点,将2个靶点集导入Cytoscape软件做交集,通过筛选拓扑特征值获取茯苓-白术药对治疗胃癌的核心靶点集,构建蛋白质-蛋白质相互作用(PPI)网络。并进行基因本体(GO)及京都基因和基因组百科全书(KEGG)富集分析。最后,通过体外实验对有效靶点及通路进行验证。结果:茯苓-白术药对含有36个有效活性成分,PPI网络关键靶点主要为MAPK3、PTGS2、EGFR、MAPK8、MAPK14、PPARG、ESR1等。预测茯苓-白术药对活性成分通过“Viral carcinogenesis”“PI3K-AKT signaling pathway”“Proteoglycans in cancer”等信号通路发挥作用。结论:茯苓-白术药对通过多成分、多靶点、多途径治疗胃癌,可通过靶向于PI3K-AKT信号通路及促分裂原活化的蛋白激酶3蛋白表达参与细胞增殖、侵袭,为进一步研究茯苓-白术药对治疗胃癌奠定了坚实基础。 |
English Summary: |
To explore the mechanism of Poria-Atractylodis Macrocephalae Rhizoma drug pair(P-AMR) in the treatment of gastric cancer(GC) by network pharmacology and experimental verification.Methods:Based on oral bioavailability and drug-likeness,the active components were obtained and screened out from Traditional Chinese Medicines Systems Pharmacology(TCMSP).All potential targets of P-AMR were predicted by Swiss Target Prediction database.Targets of GC were collected from the DisGeNET database.The two targets were imported into Cytoscape for intersection,and the core targets were identified by screening out the topological feature values.The protein-protein interaction(PPI) network was constructed.Meanwhile,the Gene Ontology(GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were conducted.The effective targets and pathways were verified by in vitro experiments.Results:A total of 36 active components of P-AMR were confirmed through using the network pharmacology method.The key proteins in the PPI network included mitogen-activated protein kinase(MAPK) 3,prostaglandin-endoperoxide synthase 2(PTGS2),epidermal growth factor receptor(EGFR),MAPK8,MAPK14,peroxisome proliferators-activated receptor-G(PPARG),estrogen receptor 1(ESR1),etc.It was predicted that P-AMR exerted effects on the active components through viral carcinogenesis,phosphoinositide 3-kinase-protein kinase B(PI3K-AKT) signaling pathway,proteoglycans in cancer,and other signaling pathways.Conclusion:P-AMR treats GC in a multi-component,multi-target,and multi-pathway manner,which can participate in the proliferation and invasion of cells by targeting the PI3K-AKT signaling pathway and the protein expression of MAPK3.This study lays a solid foundation for further research on P-AMR in the treatment of GC. |
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