首页|基于靶点网络与分子对接探讨苦参介导NF-κB通路抗肝癌的作用机制

基于靶点网络与分子对接探讨苦参介导NF-κB通路抗肝癌的作用机制

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目的:运用网络药理学及分子对接的方法,探讨苦参Sophora flavescen Ait.中有效活性成分抗肝癌(hepatocellular carcinoma,HCC)的作用机制,并通过体内、体外实验对苦参抗肝癌的作用机制进行探究.方法:通过TCMSP、Swiss Target Prediction数据库和Genecards数据库和OMIM数据库等搜集苦参的有效活性成分和治疗HCC的潜在靶点;通过STRING数据平台构建靶点基因PPI网络,将degree值排序后筛选关键靶点;通过DAVID数据平台选取关键靶点的基因进行GO和KEGG通路富集分析;通过Discovery Studio筛选后选取CASP3、STAT3作为关键靶点与前5个活性成分进行分子对接;并运用体内、体外对应性实验对网络药理学所预测的结果进行苦参抗肝癌的药效学验证.结果:网络药理学结果筛选得到39个活性成分,涉及46个关键靶点,根据度值筛选,发现前20个基因主要富集在"癌症通路"等相关通路上,分子对接试验证明关键靶点NF-KBp65、CASP3、STAT3与有效活性成分之间存在较好的亲和力.苦参抗肝癌的实验结果显示,通过抑制NF-κBp65及其相关因子TNF-α、IL-6促进肝癌细胞凋亡.结论:该研究表明苦参可通过多种成分、不同靶点激活多条通路来发挥对肝癌细胞的拮抗机制,为阐明苦参抗肝癌的分子机制提供药理学数据参考.
Exploring the Mechanism of Sophora Flavescens Mediated NF-κB Pathway Against Hepatocellular Based on Target Network and Molecular Docking
Objective:The present study aimed to explore the mechanism of the effective active ingredients in Sophora flavescens in resisting hepatocellular carcinoma(HCC)through network pharmacology,molecular docking,vivo and vitro experiments.Methods:The effective active ingredients of Sophora flavescens and potential targets for the treatment of HCC from TCMSP Database,SwissTarget-Prediction Database,GeneCards and Online Mendelian Inheritancein Man(OMIM).The protein-protein interaction(PPI)network of the common targets was constructed by STRING,and the key targets were sorted and filtered out according to the node degree.GO and KEGG pathway enrichment analysis of key target genes were selected through the DAVID data platform.Through Discovery Studio,CASP3 and STAT3 were selected as the key targets for molecular docking with the first five active components.Finally,HepG2 liver cancer cells were selected for in vivo and in vitro experiments to study the anticancer mechanism of Sophora sophora.Results:The results showed that 39 active ingredients were screened,and 46 key targets were involved.Filtering based on degree values,the research has found that the top 20 genes are mainly enriched in related pathways such as the"cancer pathway".Molecular docking experiments showed that there was a good affinity between the key targets NF-κBp65,CASP3,STAT3 and the effective active components.The ex-perimental results of anti-hepatocellular carcinoma of Sophora flavescens showed that it promoted the apoptosis of hepatocellular carcinoma cells by inhibiting NF-κBp65 and its related factors TNF-α and IL-6.Conclusion:This study indicates that Sophora flavescens can treat HCC through multiple components,different targets,and multiple pathways,providing pharmacological data reference for elucidating the molecular mechanism of Sophora flavescens in treating HCC.

Sophora flavescen AitAnti-hepatomaNetwork pharmacologyMolecular dockingMechanism

解琬迎、陆禹冰、郭晓敏、武艺、周顺、张琦、蒋希成、王赫、张乔

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哈尔滨商业大学药学院(黑龙江哈尔滨 150076)

抗肿瘤天然药物教育部工程研究中心(黑龙江哈尔滨 150076)

黑龙江中医药大学(黑龙江哈尔滨 150040)

哈尔滨医科大学附属肿瘤医院 介入科(黑龙江 哈尔滨 150040)

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苦参 抗肝癌 网络药理学 分子对接 作用机制

国家大学生创新创业训练计划项目国家自然科学基金黑龙江省省属本科高校基本科研业务费科研项目黑龙江中医药管理局中医药项目

20231024006121742612023-KYYWF-1026ZHY2022-046

2024

黑龙江医药
黑龙江省药品审评认证中心

黑龙江医药

影响因子:0.597
ISSN:1006-2882
年,卷(期):2024.37(4)
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