结合RNA测序数据分析、网络药理学和分子对接技术研究夏枯草治疗非小细胞肺癌的机制。
Combination of RNA-sequencing data analysis, network pharmacology, molecular docking techniques to investigate the mechanism of Prunella vulgaris L. in the treatment of non-small cell lung cancer.
作者信息
Dan Yanggang, Jin Yangli, Wang Jing, Wang Lu, Zheng Dawei
机构信息
Department of Thoracic Surgery, Lihuili Hospital Affiliated to Ningbo University, Ningbo, Zhejiang, China.
Department of Ultrasonography, Ningbo Yinzhou No. 2 Hospital, Ningbo, Zhejiang, China.
出版信息
Discov Oncol. 2025 May 12;16(1):726. doi: 10.1007/s12672-025-02563-7.
BACKGROUND
Prunella vulgaris L. (PVL) extracts have been reported to inhibit the proliferation and promote the apoptosis of lung cancer cells. However, its pharmacological mechanism remains unclear. The objective of this study was to explore the main active ingredients and potential molecular mechanisms of PVL in the treatment of non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS
The differentially expressed genes (DEGs) associated with NSCLC were obtained by analyzing microarray dataset GSE136043 in Gene Expression Omnibus. The bioactive components of PVL were obtained using TCMSP database, and the related targets of PVL were collected using the Swiss Target Prediction database, and drug-disease common targets were subsequently obtained. Protein-protein interaction (PPI) network was constructed using a STRING database and core targets were obtained via Cytoscape 3.9.0 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the common targets were performed using DAVID database. Molecular docking analysis was then performed using AutoDock Vina software. Finally, the therapeutic activity of morin, a crucial component of PVL, against NSCLC was verified by in vitro experiments.
RESULTS
A total of 11 active components and 180 targets of PVL were obtained, 39 of which overlapped with NSCLC's disease targets, and were considered to be "drug-disease" common targets. Morin, luteolin, delphinidin, kaempferol and quercetin were considered key components of PVL in NSCLC treatment. AKT1, MMP9, ESR1, XDH, MAPT, and CYP1B1 were considered to be the core targets in the PPI network. These "drug-disease" common targets were associated with 100 GO items, including 41 biological processes, 16 cellular components, and 43 molecular functions. KEGG enrichment analysis identified 14 signaling pathways. The key components morin, luteolin, delphinidin, kaempferol and quercetin had good binding affinity with the core targets (AKT1, MMP9, ESR1, XDH and CYP1B1). Additionally, morin could inhibit NSCLC cell viability and promote cell apoptosis in a dose-dependent manner. In addition, morin could also reduce mRNA expression levels of core targets.
CONCLUSION
PVL may have the potential to treat NSCLC with a multi-component, multi-target and multi-pathway manner.
背景
据报道，夏枯草提取物可抑制肺癌细胞增殖并促进其凋亡。然而，其药理机制尚不清楚。本研究的目的是探讨夏枯草治疗非小细胞肺癌（NSCLC）的主要活性成分和潜在分子机制。
材料与方法
通过分析基因表达综合数据库中的微阵列数据集GSE136043，获得与NSCLC相关的差异表达基因（DEG）。利用中药系统药理学数据库与分析平台（TCMSP）数据库获取夏枯草的生物活性成分，并使用瑞士靶点预测数据库收集夏枯草的相关靶点，随后获得药物 - 疾病共同靶点。使用STRING数据库构建蛋白质 - 蛋白质相互作用（PPI）网络，并通过Cytoscape 3.9.0软件获得核心靶点。使用DAVID数据库对共同靶点进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。然后使用AutoDock Vina软件进行分子对接分析。最后，通过体外实验验证了夏枯草的关键成分桑色素对NSCLC的治疗活性。
结果
共获得夏枯草的11种活性成分和180个靶点，其中39个与NSCLC的疾病靶点重叠，被认为是“药物 - 疾病”共同靶点。桑色素、木犀草素、飞燕草素、山奈酚和槲皮素被认为是夏枯草治疗NSCLC的关键成分。AKT1、MMP9、ESR1、XDH、MAPT和CYP1B1被认为是PPI网络中的核心靶点。这些“药物 - 疾病”共同靶点与100个GO条目相关，包括41个生物过程、16个细胞成分和43个分子功能。KEGG富集分析确定了14条信号通路。关键成分桑色素、木犀草素、飞燕草素、山奈酚和槲皮素与核心靶点（AKT1、MMP9、ESR1、XDH和CYP1B1）具有良好的结合亲和力。此外，桑色素可抑制NSCLC细胞活力，并以剂量依赖性方式促进细胞凋亡。此外，桑色素还可降低核心靶点的mRNA表达水平。
结论
夏枯草可能具有以多成分、多靶点和多途径方式治疗NSCLC的潜力。
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