基于网络药理学及分子对接技术探讨石斛抗肺癌潜在作用机制
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R285;R734.2

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国家自然科学基金项目(82104304);湖南省自然科学基金项目(2022JJ40224);湖南省教育厅科研项目重点项目(23A0090);湖南 省卫健委科研项目(202103021291)


Exploration on Potential Action Mechanism of Dendrobii Caulis in Anti-Lung Cancer Therapy Based on Network Pharmacology and Molecular Docking Techniques
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    摘要:

    目的:运用网络药理学及分子对接技术筛选石斛的有效活性成分及其潜在靶点,揭示石斛抗肺癌 的作用机制。方法:采用BATMAN-TCM 数据库筛选石斛活性成分及其对应的潜在靶点;在GeneCards、 OMIM、TTD、PharmGkb、DrugBank数据库中筛选肺癌相关基因;利用Venny2.1获取活性成分靶点与肺癌靶点 的交集;使用Cytoscape 3.7.2软件对数据进行可视化处理,得到石斛活性成分-靶点-肺癌网络图;通过String 数据库构建蛋白质-蛋白质相互作用(PPI) 网络,运用Metascape对潜在靶点进行基因本体(GO) 功能和京都 基因与基因组百科全书(KEGG) 通路富集分析;使用Vina软件完成分子对接并评估蛋白结合的稳定性,得到 3D结合模型;利用UALCAN、Kaplan-Meier Plotter数据库对核心靶基因的表达及预后进行分析。结果:筛选得 到60个潜在作用靶点,与15 217个肺癌相关靶点取交集,得到57个共同作用靶点。GO功能富集分析显示石斛 抗肺癌调控的生物过程主要集中在离子转运、信号转导活化、钙离子浓度调控上。KEGG信号通路富集分析提 示石斛参与调控钙信号通路、cAMP信号通路、脂肪酸代谢、PPAR信号通路及癌症途径等多条通路。通过蛋 白互作分析得到4个核心基因,分别为大麻素受体-1基因(CNR1)、糖皮质激素受体基因(NR3C1)、肿瘤坏 死因子(TNF)、前列腺素内过氧化物合酶2基因(PTGS2)。分子对接进一步验证了石斛有效活性成分(石斛 菲醌、齿叶黄皮素、24-羟基-11-脱氧甘草次酸) 与以上4个核心基因的结合稳定性。CNR1、NR3C1、PTGS2 在肺癌组织及癌旁组织中的表达均存在显著差异。生存分析结果显示CNR1、NR3C1、PTGS2高表达组总体生 存期(OS) 均长于低表达组。结论:石斛活性成分可能主要通过作用于CNR1、NR3C1、TNF、PTGS2基因调 控机体细胞周期蛋白和激酶的表达水平,或抑制炎症因子的产生和释放,从而发挥抗肺癌作用。

    Abstract:

    Abstract: Objective: To screen the active components and potential targets of Dendrobii Caulis by network pharmacology and molecular docking techniques,and to reveal the action mechanism of Dendrobii Caulis's anti-lung cancer effects. Methods:The BATMAN-TCM database was used to screen the active components of Dendrobii Caulis and their corresponding potential targets. Lung cancer-related genes were screened from the GeneCards, OMIM, PharmGkb,TTD,and DrugBank databases. Venny2.1 was used to obtain the intersection of active component targets and lung cancer targets;Cytoscape 3.7.2 software was used for data visualization to create an active component-targetlung cancer network diagram of Dendrobii Caulis; the String database was used to construct a protein-protein interaction( PPI) network,and Metascape was used for Gene Ontology( GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of potential targets;Vina software was used for molecular docking to determine the minimum free energy and obtain 3D binding models. The UALCAN and Kaplan-Meier Plotter databases were used to analyze the expression of core target genes and the prognosis. Results:A total of 60 potential targets were screened,and 57 common targets were obtained by intersecting with 15 217 lung cancer-related targets. GO functional enrichment analysis showed that the biological processes regulated by Dendrobii Caulis in anti-lung cancer mainly focused on ion transport, signal transduction activation, and calcium ion concentration regulation. KEGG pathway enrichment analysis suggested that Dendrobii Caulis is involved in regulating multiple pathways, including calcium signaling pathway, cAMP signaling pathway, fatty acid metabolism, PPAR signaling pathway, and cancer pathways. Protein interaction analysis identified four core genes: cannabinoid receptor 1 (CNR1), glucocorticoid receptor (NR3C1), tumor necrosis factor (TNF), and prostaglandin-endoperoxide synthase 2 (PTGS2). Molecular docking further verified the binding stability of Dendrobii Caulis's active components (Denbinobin, Dentatin, 24- hydroxy-11-deoxoglycyrrhetinic acid) with these four core genes. CNRL, NR3C1, PTGS2 showed significant differences between lung cancer tissues and tissues adjacent to cancer. Survival analysis indicated that the overall survival (OS) of the high expression groups of CNR1,NR3C1,and PTGS2 was longer than that of the low expression groups. Conclusion: The active components of Dendrobii Caulis may exert their anti-lung cancer effects mainly by regulating the expression levels of cellular cyclins and kinases through acting on CNR1,NR3C1,TNF,and PTGS2 genes,or inhibiting the production and release of inflammatory factors.

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戴鹏辉,张晨彬,陈韬,施远香.基于网络药理学及分子对接技术探讨石斛抗肺癌潜在作用机制[J].新中医,2025,57(6):100-108

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  • 在线发布日期: 2025-03-26
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