首页|基于整合药理学探讨"茯苓-甘草"协同配伍对肺腺癌的作用机制及验证研究

基于整合药理学探讨"茯苓-甘草"协同配伍对肺腺癌的作用机制及验证研究

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目的:基于网络药理学和生物信息学探讨"茯苓-甘草"协同配伍对肺腺癌的作用机制及靶点,并通过实验验证"茯苓-甘草"主要成分槲皮素对肺腺癌的抑制作用.方法:对肺腺癌相关基因进行差异分析,从TCMSP数据库下载"茯苓-甘草"有效成分及靶标,获取药物-疾病共同靶标,进行网络构建、富集分析、生存分析等.通过对"茯苓-甘草"主要成分与肺腺癌关键靶点进行分子对接,选出构效关系良好的有效成分进行后续实验验证.通过细胞增殖、划痕及侵袭实验检测药物对肺腺癌细胞的干预作用,实时荧光定量法检测药物对关键靶点的作用.结果:肺腺癌8 109个差异表达基因和102个药物靶基因取交集共获得32个共同基因,富集分析显示靶基因主要参与p53信号通路、细胞衰老等癌症相关通路,分子对接结果显示槲皮素具有良好的构效关系,因此选择槲皮素进行后续实验验证.有效成分槲皮素可以抑制肺腺癌A549及H1299细胞的增殖、迁移及侵袭能力,并且可以显著下调关键靶点含杆状病毒IAP重复序列蛋白5(BIRC5)、细胞周期蛋白B1(CCNB1)、检查点蛋白激酶1(CHEK1)的表达.结论:"茯苓-甘草"有效成分槲皮素可以有效抑制肺腺癌恶性表型,其机制可能与靶向调节关键基因BIRC5、CCNB1、CHEK1的表达有关.
Mechanism and Validation of Synergistic Compatibility of "Fuling(Poria)-Gancao(Glycyrrhizae Radix Et Rhizoma)" on Lung Adenocarcinoma Based on Integrated Pharmacology
Objective:To investigate the mechanism and targets of synergistic compatibility of"Fuling(Poria)-Gancao(Glycyrrhizae Radix Et Rhizoma)"on lung adenocarcinoma based on network pharmacology and bioinformatics,and to verify the inhibitory effect of quercetin,the main ingredient of"Fuling-Gancao",on lung adenocarcinoma through experiments.Methods:Differential analysis of lung adenocarcinoma related genes was performed.The active ingredients and targets of"Fuling-Gancao"was downloaded from TCMSP database.And the drug-disease common targets were obtained for network construction,enrichment analysis and survival analysis.Through molecular docking between the main ingredients of"Fuling-Gancao"and the key targets of lung adenocarcinoma,the effective ingredients with good structure-activity relationship were selected for subsequent experimental validation.The intervention effects of the drugs on lung adenocarcinoma cells were detected by cell proliferation,scratch and invasion assays,and the effects of the drugs on key targets were detected by real-time fluorescence quantitative.Results:A total of 32 common genes were obtained by taking the intersection of 8 109 differentially expressed genes and 102 drug target genes in lung adenocarcinoma.Enrichment analysis showed that the target genes were mainly involved in p53 signaling pathway,cellular senescence,and other cancer-related pathways.And the results of molecular docking showed that quercetin had a good structure-activity relationship.Therefore,quercetin was selected for subsequent experimental verification.The active ingredient quercetin can inhibit the proliferation,migration and invasion ability of lung adenocarcinoma A549 and H1299 cells,and can significantly down-regulate the expression of the key targets BIRC5,CCNB1 and CHEK1.Conclusions:Quercetin,the active ingredient of"Fuling-Gancao",can effectively inhibit the malignant phenotype of lung adenocarcinoma.Its mechanism may be related to the targeted regulation of the expression of key genes BIRC5,CCNB1 and CHEK1.

Fuling(Poria)Gancao(Glycyrrhizae Radix Et Rhizoma)quercetinnetwork pharmacologybioinfor-maticslung adenocarcinoma

钟玉婷、商琳晓、姚燕、张文峰、孙长岗

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山东中医药大学第一临床医学院,山东济南 250355

滨州医学院中西医结合学院,山东烟台 264003

澳门科技大学中医药学院,澳门 999078

潍坊市中医院肿瘤科,山东潍坊 261041

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茯苓 甘草 槲皮素 网络药理学 生物信息学 肺腺癌

国家自然科学基金面上项目国家自然科学基金面上项目

8217422281973677

2024

山东中医药大学学报
山东中医药大学

山东中医药大学学报

CSTPCD
影响因子:0.52
ISSN:1007-659X
年,卷(期):2024.48(1)
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