白藜芦醇治疗非小细胞肺癌机制的网络药理学分析及实验验证
R734.2; 目的:采用网络药理学和分子对接技术识别分析白藜芦醇抗非小细胞肺癌(NSCLC)的潜在靶点和作用机制,并结合临床数据以及分子生物学实验进行初步验证.方法:通过Swiss Target Prediction数据库和Target net数据库筛选白藜芦醇靶点,通过数据库Genecards、OMIM、TTD收集NSCLC靶点,利用Venny 2.1.0平台获得药物和疾病靶点的交集;应用Cytoscape 3.7.2软件与String数据库生成靶标蛋白互作网络(PPI),并进行拓扑分析;利用Metascape数据库对交集靶标进行基因本体(GO)功能富集与京都基因与基因组百科全书(KEGG...
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| Published in | 食品工业科技 Vol. 45; no. 1; pp. 28 - 36 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | Chinese |
| Published |
山西医科大学基础医学院,山西太原 030001%山西医科大学第一临床医学院,山西太原 030001%山西医科大学第二医院,山西太原 030000
2024
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1002-0306 |
| DOI | 10.13386/j.issn1002-0306.2023030048 |
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| Abstract | R734.2; 目的:采用网络药理学和分子对接技术识别分析白藜芦醇抗非小细胞肺癌(NSCLC)的潜在靶点和作用机制,并结合临床数据以及分子生物学实验进行初步验证.方法:通过Swiss Target Prediction数据库和Target net数据库筛选白藜芦醇靶点,通过数据库Genecards、OMIM、TTD收集NSCLC靶点,利用Venny 2.1.0平台获得药物和疾病靶点的交集;应用Cytoscape 3.7.2软件与String数据库生成靶标蛋白互作网络(PPI),并进行拓扑分析;利用Metascape数据库对交集靶标进行基因本体(GO)功能富集与京都基因与基因组百科全书(KEGG)通路富集分析,得到交集靶标的基因图谱;利用Autodock Vina软件对排名前三位的核心靶基因与白藜芦醇进行分子对接验证;通过癌症基因组图谱(TCGA)数据库获得临床病例样本,分析相关靶基因在NSCLC患者(n=1017)和健康人群(n=627)的表达情况;细胞水平采用Western Blot检测不同浓度(30、50 μmol/L)白藜芦醇对人肺腺癌A549细胞SRC、EGFR及PI3K/AKT信号通路蛋白表达的影响.结果:筛选得到的潜在靶点共有 40个,经过拓扑分析得到关键靶点 8个,其中EGFR、SRC、ESR1等靶点与NSCLC密切相关;白藜芦醇抗NSCLC主要涉及肿瘤蛋白多糖、雌激素信号通路、PI3K/AKT等多条信号通路;分子对接显示,白藜芦醇与关键靶点具有稳定的结合能力;临床样本结果显示,靶基因EGFR、SRC、ESR1、HSP90AA1以及MMP9的表达在NSCLC中上调;TNF、CDC42以及RELA的表达在NSCLC中下调;细胞实验结果表明,白藜芦醇药物干预以剂量依赖的方式抑制了人肺腺癌A549细胞中SRC、EGFR、p-PI3K和p-AKT的蛋白表达.结论:揭示了白藜芦醇在治疗NSCLC的过程中涉及多个作用靶点及多条信号通路,明确了白藜芦醇可通过抑制PI3K/AKT信号通路发挥其抗癌效应. |
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| AbstractList | R734.2; 目的:采用网络药理学和分子对接技术识别分析白藜芦醇抗非小细胞肺癌(NSCLC)的潜在靶点和作用机制,并结合临床数据以及分子生物学实验进行初步验证.方法:通过Swiss Target Prediction数据库和Target net数据库筛选白藜芦醇靶点,通过数据库Genecards、OMIM、TTD收集NSCLC靶点,利用Venny 2.1.0平台获得药物和疾病靶点的交集;应用Cytoscape 3.7.2软件与String数据库生成靶标蛋白互作网络(PPI),并进行拓扑分析;利用Metascape数据库对交集靶标进行基因本体(GO)功能富集与京都基因与基因组百科全书(KEGG)通路富集分析,得到交集靶标的基因图谱;利用Autodock Vina软件对排名前三位的核心靶基因与白藜芦醇进行分子对接验证;通过癌症基因组图谱(TCGA)数据库获得临床病例样本,分析相关靶基因在NSCLC患者(n=1017)和健康人群(n=627)的表达情况;细胞水平采用Western Blot检测不同浓度(30、50 μmol/L)白藜芦醇对人肺腺癌A549细胞SRC、EGFR及PI3K/AKT信号通路蛋白表达的影响.结果:筛选得到的潜在靶点共有 40个,经过拓扑分析得到关键靶点 8个,其中EGFR、SRC、ESR1等靶点与NSCLC密切相关;白藜芦醇抗NSCLC主要涉及肿瘤蛋白多糖、雌激素信号通路、PI3K/AKT等多条信号通路;分子对接显示,白藜芦醇与关键靶点具有稳定的结合能力;临床样本结果显示,靶基因EGFR、SRC、ESR1、HSP90AA1以及MMP9的表达在NSCLC中上调;TNF、CDC42以及RELA的表达在NSCLC中下调;细胞实验结果表明,白藜芦醇药物干预以剂量依赖的方式抑制了人肺腺癌A549细胞中SRC、EGFR、p-PI3K和p-AKT的蛋白表达.结论:揭示了白藜芦醇在治疗NSCLC的过程中涉及多个作用靶点及多条信号通路,明确了白藜芦醇可通过抑制PI3K/AKT信号通路发挥其抗癌效应. |
| Abstract_FL | Objective:To explore the potential therapeutic targets and mechanisms of resveratrol in the treatment of non-small cell lung cancer(NSCLC),a comprehensive study was conducted incorporating network pharmacology,molecular docking methods,and experimental validation.Methods:The targets of resveratrol were searched on Swiss Target Prediction database and Target net database.NSCLC targets were gathered from Genecards,OMIM,TTD databases.The intersection of drug targets and disease targets was obtained using Venny 2.1.0 platform.Next,Cytoscape 3.7.2 software was applied along with the String database to generate target protein interaction networks(PPI)and perform topological analysis.GO functional enrichment analysis and KEGG pathway enrichment analysis of intersecting targets were conducted using the Metascape database,resulting in gene maps of the intersecting targets.Molecular docking studies were performed for the top three ranked core targets and resveratrol using Autodock Vina software.Clinical case samples were obtained from The Cancer Genome Atlas(TCGA)database to analyze the expression of relevant targets in NSCLC patients(n=1017)and healthy controls(n=627).The effects of different concentrations(30 and 50 μmol/L)of resveratrol on the protein expression of SRC,EGFR and PI3K/AKT signaling pathway in human lung adenocarcinoma A549 cells were examined using Western Blot at the cellular level.Results:Total of 40 potential targets were screened out,followed by obtaining 8 key targets after topological analysis.These keys targets,including EGFR,SRC,and ESR1 were closely associated with NSCLC.The treatment of NSCLC with resveratrol primarily involved multiple signaling pathways,such as tumor proteoglycans,estrogen signaling and PI3K/AKT.Molecular docking results demonstrated that resveratrol had a good binding ability with the target protein.Clinical sample results revealed that the expression of EGFR,SRC,ESR1,HSP90AA1,and MMP9 was upregulated,while the expression of TNF,CDC42,and RELA was downregulated in NSCLC patients.Cellular experiments indicated that resveratrol could inhibit the protein expression of SRC,EGFR,p-PI3K,and p-AKT in human lung adenocarcinoma A549 cells in a dose-dependent manner.Conclusion:This study demonstrates that resveratrol involves multiple targets and signaling pathways in the treatment of NSCLC,and clarifies that resveratrol could exert its anti-cancer effects by inhibiting the PI3K/AKT signaling pathway. |
| Author | 钮宇恒 刘清华 张羽 霍如婕 田新瑞 董杨逗 |
| AuthorAffiliation | 山西医科大学基础医学院,山西太原 030001%山西医科大学第一临床医学院,山西太原 030001%山西医科大学第二医院,山西太原 030000 |
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| Author_FL | NIU Yuheng ZHANG Yu HUO Rujie TIAN Xinrui LIU Qinghua DONG Yangdou |
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| DocumentTitle_FL | Exploring the Mechanism of Action of Resveratrol in the Treatment of Non-small Cell Lung Cancer Based on Network Pharmacology and Experimental Validation |
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| Keywords | 网络药理学 non-small cell lung cancer the cancer genome atlas 白藜芦醇 癌症基因组图谱 network pharmacology PI3K/AKT signaling pathway PI3K/AKT信号通路 非小细胞肺癌 resveratrol |
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| Publisher | 山西医科大学基础医学院,山西太原 030001%山西医科大学第一临床医学院,山西太原 030001%山西医科大学第二医院,山西太原 030000 |
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| Snippet | R734.2; 目的:采用网络药理学和分子对接技术识别分析白藜芦醇抗非小细胞肺癌(NSCLC)的潜在靶点和作用机制,并结合临床数据以及分子生物学实验进行初步验证.方法:通过Swiss... |
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| Title | 白藜芦醇治疗非小细胞肺癌机制的网络药理学分析及实验验证 |
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