{"title":"Comprehensive analysis of the potential mechanism of gansui in blocking non-small cell lung cancer progression.","authors":"Xiaoxu Yang, Wenlan Li","doi":"10.1080/13880209.2025.2471844","DOIUrl":null,"url":null,"abstract":"<p><strong>Context: </strong>Gansui [<i>Euphorbia kansui</i> T. N. Liou ex S.B.Ho (Euphorbiaceae)] has been reported to inhibit the proliferation of non-small cell lung cancer (NSCLC) cells; however, its underlying pharmacological mechanism remains unclear.</p><p><strong>Objective: </strong>To investigate the potential effects and mechanisms of Gansui in blocking NSCLC progression.</p><p><strong>Materials and methods: </strong>The targets of Gansui's components and NSCLC-related targets were obtained through public database and published studies. Functional enrichment analysis was performed using the clusterProfiler R package. STRING database was used for protein-protein interaction analysis. CytoHubba plugin was applied to get the hub genes. Molecular docking was applied to assess the binding affinities between the hub targets and the crucial components. Kidjolanin was used to treat A549 and NCI-H1385, and its effects on cell viability, sensitivity of paclitaxel and expression levels of hub genes were investigated by cell counting kit-8 assay, flow cytometry and qPCR.</p><p><strong>Results: </strong>A total of 16 Gansui active ingredients and 337 targets were collected, of which 298 targets overlapped with NSCLC-related genes. <i>STAT3</i>, <i>EGFR</i>, <i>GRB2</i>, <i>AKT2, AKT3</i> and <i>PIK3CA</i> were identified as hub genes. The components in Gansui, including kidjoranin 3-O-β-digitoxopyranoside, cynotophylloside B, 13-Oxyingenol-dodecanoate, and kidjolanin had good binding affinity with the hub targets. Kidjolanin inhibited the viability of NSCLC cells, promoted apoptosis and inhibited the expression of hub genes. Kidjolanin also enhanced the proliferation inhibition and apoptosis of NSCLC cells induced by paclitaxel.</p><p><strong>Discussion and conclusion: </strong>Gansui exerts anti-NSCLC effects <i>via</i> multiple downstream targets, implying its potential in NSCLC treatment.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"63 1","pages":"170-187"},"PeriodicalIF":3.9000,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878171/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13880209.2025.2471844","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/3 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Context: Gansui [Euphorbia kansui T. N. Liou ex S.B.Ho (Euphorbiaceae)] has been reported to inhibit the proliferation of non-small cell lung cancer (NSCLC) cells; however, its underlying pharmacological mechanism remains unclear.
Objective: To investigate the potential effects and mechanisms of Gansui in blocking NSCLC progression.
Materials and methods: The targets of Gansui's components and NSCLC-related targets were obtained through public database and published studies. Functional enrichment analysis was performed using the clusterProfiler R package. STRING database was used for protein-protein interaction analysis. CytoHubba plugin was applied to get the hub genes. Molecular docking was applied to assess the binding affinities between the hub targets and the crucial components. Kidjolanin was used to treat A549 and NCI-H1385, and its effects on cell viability, sensitivity of paclitaxel and expression levels of hub genes were investigated by cell counting kit-8 assay, flow cytometry and qPCR.
Results: A total of 16 Gansui active ingredients and 337 targets were collected, of which 298 targets overlapped with NSCLC-related genes. STAT3, EGFR, GRB2, AKT2, AKT3 and PIK3CA were identified as hub genes. The components in Gansui, including kidjoranin 3-O-β-digitoxopyranoside, cynotophylloside B, 13-Oxyingenol-dodecanoate, and kidjolanin had good binding affinity with the hub targets. Kidjolanin inhibited the viability of NSCLC cells, promoted apoptosis and inhibited the expression of hub genes. Kidjolanin also enhanced the proliferation inhibition and apoptosis of NSCLC cells induced by paclitaxel.
Discussion and conclusion: Gansui exerts anti-NSCLC effects via multiple downstream targets, implying its potential in NSCLC treatment.
期刊介绍：
Pharmaceutical Biology will publish manuscripts describing the discovery, methods for discovery, description, analysis characterization, and production/isolation (including sources and surveys) of biologically-active chemicals or other substances, drugs, pharmaceutical products, or preparations utilized in systems of traditional medicine.
Topics may generally encompass any facet of natural product research related to pharmaceutical biology. Papers dealing with agents or topics related to natural product drugs are also appropriate (e.g., semi-synthetic derivatives). Manuscripts will be published as reviews, perspectives, regular research articles, and short communications. The primary criteria for acceptance and publication are scientific rigor and potential to advance the field.
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