Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Preferential enhancement of mitochondria-mediated apoptosis and modulation of metastasis-related markers by etoposide-loaded nanoparticles in breast cancer cell lines.","authors":"Filiz Bakar-Ates, Ceyda Tuba Sengel-Turk","doi":"10.1007/s00210-026-05676-0","DOIUrl":"10.1007/s00210-026-05676-0","url":null,"abstract":"<p><p>Etoposide is a widely used chemotherapeutic agent whose clinical application is limited by systemic toxicity and suboptimal intracellular delivery. Lipid-polymer hybrid nanoparticles have emerged as promising drug delivery systems that combine structural stability with enhanced cellular interaction. This study aimed to evalute the apoptotic and metastasis-related effects of etoposide-loaded lipid-polymer hybrid nanoparticles (ET-NPs) against human breast cancer cells. ET-NPs were synthesized and characterized, and their biological effects were compared with free etoposide in MCF-7 and MDA-MB-231 breast cancer cell lines. Cell viability was assessed using the MTT assay. Cell cycle distribution, Annexin V binding activity, mitochondrial membrane potential, and caspase activation were analyzed by flow cytometry based Muse Cell Analyzer. MMP-2 and MMP-9 mRNA levels were determined by quantitative real-time PCR. ET-NPs significantly enhanced the cytotoxic and pro-apoptotic effects of etoposide in both breast cancer cell lines. Annexin V analysis demonstrated increased apoptotic cell populations following ET-NP treatment compared with free etoposide. ET-NP also induced significant mitochondrial membrane depolarization, caspase activation, and G2/M phase arrest. Furthermore, ET-NP significantly exerted potential anti-metastatic activity indicating a preferential antitumor effect in MCF-7 cells compared with MDA-MB-231 cells. The findings of this study demonstrate that lipid-polymer hybrid nanoparticle-mediated delivery enhances the anticancer efficacy of etoposide in breast cancer cells by potentiating apoptotic signaling and suppressing metastasis-related gene expression. ET-NP may therefore represent a promising nanotherapeutic strategy for improving breast cancer treatment outcomes.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"20477-20492"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simvastatin enhances the antitumor activity of temsirolimus through AMPK-associated metabolic modulation in clear-cell renal cell carcinoma.","authors":"Hsuan-Yu Chen, Chien-Jui Cheng, Te-Hsing Hsu, Szu-Yu Tung, Fang-Ning Chou, Mantosh Kumar Satapathy, Shu-Hui Juan","doi":"10.1007/s00210-026-05733-8","DOIUrl":"10.1007/s00210-026-05733-8","url":null,"abstract":"<p><p>Clear-cell renal cell carcinoma (ccRCC) is characterized by VHL-associated metabolic reprogramming, including enhanced glycolysis and lipid biosynthesis, which may create therapeutic vulnerabilities. However, mTOR inhibitors such as temsirolimus often show limited efficacy due to adaptive metabolic compensation. We investigated whether simvastatin-induced metabolic stress enhances sensitivity to mTOR inhibition in a context-dependent manner in ccRCC. VHL-mutant (A498) and VHL-wild-type (Caki1) ccRCC cells were treated with simvastatin and temsirolimus, alone or in combination. Cell viability, colony formation, migration, Seahorse metabolic flux analysis, and Western blotting were performed. Mechanistic studies included shRNA-mediated knockdown of LKB1/AMPKα1/α2 and pharmacological modulation using Compound C and AICAR. Antitumor efficacy was evaluated in a Caki1 subcutaneous xenograft model in nude mice. Temsirolimus induced modest growth inhibition, whereas simvastatin produced stronger dose- and time-dependent effects. Combination treatment (simvastatin 2.5 µM + temsirolimus 100 nM) further reduced cell viability. Interaction analysis revealed a cell-dependent response, with synergism in A498 cells (combination index (CI), 0.31-0.77) and antagonistic-to-additive effects in Caki1 cells (CI, 1.6-2.7). Mechanistically, simvastatin activated LKB1-AMPK signaling, suppressed AKT/mTOR activity, reduced glycolysis (↓pPFKFB2), increased FBP1 expression, and downregulated lipid biosynthesis enzymes (FASN, SCD), thereby promoting ER stress and apoptosis. In vivo, combination therapy significantly suppressed tumor growth compared with monotherapy and alleviated temsirolimus-induced hypercholesterolemia without apparent toxicity. Simvastatin-induced metabolic perturbation enhances mTOR inhibition in a cell-dependent manner, supporting dual metabolic targeting as a potential therapeutic strategy in ccRCC.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"21639-21652"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Luteolin alleviates inflammation by inhibiting the PI3K-Akt-FOXO3a pathway.","authors":"Leyuan Zeng, Jinxian Lu, Ronghua Liu, Junwei He, Li Yang","doi":"10.1007/s00210-026-05722-x","DOIUrl":"10.1007/s00210-026-05722-x","url":null,"abstract":"<p><p>Luteolin is a flavonoid commonly found in various plants and has been shown to possess a wide range of biological activities through the modulation of multiple signaling pathways. Despite its well-documented effects, the underlying molecular mechanism responsible for its anti-inflammatory properties remains unclear. Network pharmacology suggested that luteolin may exert anti-inflammatory effects by modulating the PI3K/Akt/FOXO3a signaling cascade. Consistent with this prediction, in an LPS-stimulated RAW264.7 macrophage model, luteolin significantly decreased the phosphorylation of PI3K, Akt, and FOXO3a, while also lowering the ratios of p-PI3K/PI3K, p-Akt/Akt, and p-FOXO3a/FOXO3a. Additionally, Molecular docking combined with molecular dynamics simulations indicated that luteolin can bind to PI3K, Akt, and FOXO3a to form stable protein-ligand complexes, supporting the presence of strong binding affinity/interactions between luteolin and these targets. Further validation using cellular thermal shift assay, isothermal dose-response, and drug affinity response target stability techniques confirmed that luteolin directly interacts with PI3K. These results provide compelling evidence supporting luteolin's potential clinical use, enhance our understanding of the mechanisms driving inflammation, and lay the groundwork for the development of novel anti-inflammatory therapies inhibiting the PI3K-Akt-FOXO3a pathway.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"21373-21389"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of gossypetin's effects on gut microbiota profile and TLR4, Myd88, NFKB, and NLRP3 signaling pathways in rats.","authors":"Onder Akkas, Demet Celebi, Ozgur Celebi, Sumeyye Baser, Sıla Ektas Kalayci, Betül Ari, Mustafa Can Guler, Bulent Dabanlıoglu, Selahattin Celebi, Metin Kılıclıoglu, Serkan Yıldırım","doi":"10.1007/s00210-026-05717-8","DOIUrl":"10.1007/s00210-026-05717-8","url":null,"abstract":"<p><p>Gut microbiota plays a crucial role in maintaining host homeostasis by regulating metabolic processes and immune responses. Disruptions in microbial composition are closely associated with inflammatory diseases and are often linked to the activation of key signaling pathways such as Toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa TLR4/MyD88/NF-κB and NLR family pyrin domain-containing 3 (NLRP3) inflammasome. Natural bioactive compounds, particularly flavonoids, have gained attention due to their potential to modulate both gut microbiota and inflammation-related pathways. In this context, the present study aimed to evaluate the effects of gossypetin on gut microbiota composition and its regulatory role on TLR4, MyD88, NF-κB, and NLRP3 signaling pathways in a rat model. Adult female Wistar albino rats were divided into control and gossypetin-treated groups (50 mg/kg, oral gavage/56 days dose). Gut microbiota was analyzed by 16S rRNA sequencing, and protein expression levels were assessed using Western blot. Histopathological, immunohistochemical, and immunofluorescence analyses were also in liver, intestinal, and spleen tissue performed. Gossypetin administration reduced microbial diversity and altered microbiota composition, with increases in Mediterraneibacter spp., Blautia spp., and Lactobacillus spp. Western blot results showed significant decreases in NLRP3 (p ≤ 0.01) and NF-κB (p ≤ 0.05) levels, while TLR4 and MyD88 remained unchanged. Histological analyses revealed mild tissue alterations and increased oxidative stress markers. These results suggest that gossypetin modulates microbiota composition and exerts selective anti-inflammatory effects, highlighting its potential in microbiota-associated inflammatory regulation.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"21465-21480"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vildagliptin attenuates the development of CCl₄-induced liver fibrosis: associations with gut-liver axis modulation and LPS/notch-related signaling.","authors":"Aya M Eid, Ahmed O El-Gendy, Mohamed Gamal El-Din Ewees","doi":"10.1007/s00210-026-05961-y","DOIUrl":"https://doi.org/10.1007/s00210-026-05961-y","url":null,"abstract":"<p><p>Liver fibrosis is a progressive pathological condition closely linked to gut microbiota dysbiosis and impaired intestinal barrier integrity. Vildagliptin, a dipeptidyl peptidase-4 inhibitor used in type 2 diabetes, exhibits pleiotropic anti-inflammatory and antioxidant properties; however, its impact on the gut-liver axis during hepatic fibrogenesis remains insufficiently defined. This experimental study investigated whether concomitant vildagliptin administration attenuates the development of CCl₄-induced liver fibrosis and whether this effect is associated with alteration in gut microbial composition, intestinal barrier-related markers, and circulating lipopolysaccharide (LPS), and hepatic fibrosis-associated molecular changes. Male rats were allocated to five groups: normal control, Vildagliptin alone (20 mg/kg/day), CCl₄-fibrosis, and CCl₄ + Vildagliptin (10 or 20 mg/kg/day). Liver fibrosis was induced by CCl₄ administration for six weeks, with concomitant daily oral Vildagliptin in the treatment groups. Liver function indices, fibrotic markers, oxidative stress parameters, and serum LPS were assessed. Intestinal barrier-related changes were assessed by measuring colonic ZO-1 and occludin levels, while circulating LPS was quantified as a marker of systemic endotoxemia. Hepatic ADAM17, Notch-1, DNMT3A, and Smad7 protein levels and β-Klotho mRNA expression were assessed. Liver and colon histopathology was examined, and gut microbiota composition was profiled using 16S rRNA gene amplicon sequencing. Vildagliptin significantly ameliorated CCl₄-induced liver injury and fibrosis, evidenced by improved biochemical parameters, reduced collagen deposition and hydroxyproline, and attenuation of hepatic stellate cell activation. These effects were accompanied by increased colonic ZO-1 and occludin levels, reduced circulating LPS, decreased hepatic ADAM17, Notch-1, and DNMT3A protein levels, increased β-Klotho mRNA expression and Smad7 protein levels, and alterations in gut microbiota composition. Collectively, concomitant vildagliptin administration attenuated the development of CCl₄-induced liver fibrosis and was associated with modulation of gut-liver axis -related changes and alterations in LPS- and Notch-related molecular markers.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of ursolic acid-loaded cubosomal nanocarriers: enhanced dissolution, pharmacokinetics, bioavailability, and anticancer activity.","authors":"Amol Patil, Durgacharan Bhagwat, Harinath More, Vijay Kumbar, Madhu Gupta","doi":"10.1007/s00210-026-05967-6","DOIUrl":"https://doi.org/10.1007/s00210-026-05967-6","url":null,"abstract":"<p><p>Ursolic acid (UA) is a promising anticancer agent whose therapeutic application is hindered by poor aqueous solubility, limited permeability, rapid elimination, and low oral bioavailability. In this study, UA-loaded cubosomal nanoparticles (UA-CN) were developed and optimized using a three-factor, three-level Box-Behnken design. The effects of glyceryl monooleate, Poloxamer 407, and microfluidization cycles on particle size, zeta potential, and entrapment efficiency were systematically evaluated. The optimized UA-CN exhibited a particle size of 131.9 ± 4.12 nm, zeta potential of - 44.2 ± 3.67 mV, and entrapment efficiency of 96.16 ± 1.89%. FTIR, XRD, and DSC analyses supported UA incorporation into the cubosomal matrix and a reduction in its crystalline character. In vitro dissolution studies demonstrated markedly enhanced drug release from UA-CN, with approximately 90% of UA released within 24 h compared with 38% from the pure drug. Pharmacokinetic evaluation in rabbits showed an approximately six-fold increase in oral bioavailability following UA-CN administration. The optimized cubosomal formulation also exhibited enhanced anticancer activity, supporting its potential to improve the biopharmaceutical performance of UA and its utility as a nanocarrier for breast cancer therapy.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rosmarinic acid inhibits norepinephrine-induced metastatic capacity of triple negative breast cancer cells by Src kinase inactivation.","authors":"Jae-Hoon Jeong, Hyun-Ji Park, Shin-Hyung Park","doi":"10.1007/s00210-026-05677-z","DOIUrl":"10.1007/s00210-026-05677-z","url":null,"abstract":"<p><p>Chronic psychological stress promotes cancer metastasis through catecholamine-mediated activation of β-adrenergic signaling. This study aimed to evaluate the inhibitory effects of rosmarinic acid (RA) on norepinephrine (NE)-induced migration and invasion in triple-negative breast cancer (TNBC) cells and to elucidate the underlying molecular mechanisms. Cell viability was assessed using an MTT assay. Migration and invasion were evaluated by Transwell assays in MDA-MB-231 and BT-20 cells treated with NE in the presence or absence of RA. Src phosphorylation and EMT-related protein expression were analyzed by Western blotting. Molecular docking was performed to predict the binding of RA to Src kinase. Constitutively active Src transfection was used to confirm the role of Src. A network pharmacology-based analysis was conducted to identify RA-associated targets and enriched pathways. RA significantly suppressed NE-induced migration and invasion in TNBC cells. RA markedly reduced NE-induced Src phosphorylation, and docking analysis predicted stable binding of RA within the ATP-binding pocket of Src. Constitutive Src activation abrogated the anti-migratory and anti-invasive effects of RA, confirming Src as a key molecular target. RA also attenuated NE-induced EMT by reducing mesenchymal marker expression. Network pharmacology analysis revealed enrichment of RA-associated targets in cancer-related pathways and identified several hub genes that converge on Src-related signaling cascades. RA suppresses NE-induced metastatic phenotypes in TNBC cells primarily through inhibition of Src kinase and partial modulation of the EMT program, highlighting its potential as a therapeutic candidate for stress-associated TNBC metastasis.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"20465-20476"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid sono-microwave synthesis of V₂O₃ NPs: structural enhancement and Bax/Bcl-2-mediated apoptosis in cancer cells, in vitro and molecular docking insights.","authors":"Huda Mohammed Mahmoud, Sahar Salim Mohammad, Hind M Ahmed, Hiba H Ibraheem, Seham M Hussein, Duha S Ahmed","doi":"10.1007/s00210-026-05662-6","DOIUrl":"10.1007/s00210-026-05662-6","url":null,"abstract":"<p><p>V₂O₃ NPs were successfully synthesized using a sono-microwave method with NH₄VO₃ and CTAB as raw materials. The synthesized nanoparticles were characterized using XRD, FESEM, EDS, UV-Vis, and FTIR techniques, with the results confirming the formation of crystalline plate-like nanostructures with sheets ranges from 100 to 200 nm and the length of the plate is in the range of 100-500 nm. The method has apparent efficiency, simplicity, and low cost for preparing V₂O₃. Moreover, V₂O₃ NPs were displayed in a molecular docking, and the data visualized the best prediction of inhibition towards lung, breast, and colon carcinoma. The findings showed that lung cancer with ID: 2P85 evaluated a significant total binding energy of - 9.49 kcal/mol. V₂O₃ nanoparticles exhibited potent, dose-dependent cytotoxicity against A549, HT-29, and MCF-10 cancer cell lines, as confirmed by MTT assays. V₂O₃ NPs demonstrated significant anticancer activity against lung, breast, and colorectal cancer cell models after 72 h of exposure to a concentration of 40 μg/ml. The results confirmed a clear concentration-dependent cytotoxic effect, supported by a marked modulation of apoptosis-related biomarkers. V₂O₃ NPs notably increased Bax protein expression while simultaneously decreasing BCl2 levels in all treated cancer cell lines compared to untreated control samples. Consequently, the Bax/BCl2 ratio increased considerably, reaching 2.76 in HT-29 cells, 2.20 in MCF-7 cells, and 1.68 in A549 cells, a suggestion of the mitochondrial apoptotic path.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"20567-20586"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-layer network biology combined with single-cell evidence reveals core regulatory nodes in atherosclerotic plaques and potential drug-targeting directions.","authors":"Dajun Huang, Ying Liu, Yilan Wang, Jinming Hu, Hanzhang Tang, Yongjun Yin, Lingqiu Kong","doi":"10.1007/s00210-026-05672-4","DOIUrl":"10.1007/s00210-026-05672-4","url":null,"abstract":"<p><p>Atherosclerosis (AS) is driven by intertwined inflammatory responses and vascular wall remodeling, yet the core regulatory networks and actionable targets underlying plaque formation remain incompletely defined. Bulk transcriptomic data from GSE43292, comprising paired advanced carotid plaques and distant early-stage lesion tissues from 32 patients, were analyzed to identify differentially expressed genes (DEGs), followed by WGCNA and intersection with GeneCards-derived AS-related genes. Candidate genes were mapped to a STRING PPI network, and hub genes were prioritized using four Cytoscape algorithms (MCC, EPC, Stress, Degree). Functional annotation (GO/KEGG), immune infiltration, and single-gene GSEA were performed. A 10 × scRNA-seq dataset (GSE159677) was used for cell-type annotation, compositional comparison, cell-cell communication, and hub-gene localization. Drug prediction was conducted, followed by molecular docking of candidate compounds with hub proteins. Finally, an oxLDL-induced in vitro model was used for validation by CCK-8, ROS staining, Western blotting, and qRT-PCR. Seven hub genes (SMAD4, CASP8, PARP1, CRKL, CDK6, VDAC1, KHDRBS1) were identified. Enrichment analyses linked these hubs to cell death/stress regulation, immune-related programs, and vascular remodeling. Immune infiltration suggested marked immune reconfiguration in plaques. Single-gene GSEA highlighted coordinated remodeling of vascular smooth muscle contraction, gap junction signaling, and lipid/NAD-associated metabolism. scRNA-seq analysis indicated joint contributions from myeloid and vascular structural cells, with hub genes showing cell-type-biased enrichment. Quercetin emerged as a candidate compound; docking supported favorable multi-target binding (strongest for PARP1 and CDK6). Experimentally, oxLDL upregulated hub-gene mRNA/protein levels, while quercetin significantly attenuated these increases. We define an AS-associated hub-gene network with single-cell context and provide convergent computational and experimental evidence that quercetin exerts endothelial-protective effects consistent with multi-target modulation of the hub-gene network, supporting its therapeutic potential in AS.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"20587-20608"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic network analysis and functional evidence identify a candidate EMT hub signature associated with nasopharyngeal carcinoma progression.","authors":"Xiaopeng Sun, Bo Kou","doi":"10.1007/s00210-026-05675-1","DOIUrl":"10.1007/s00210-026-05675-1","url":null,"abstract":"<p><p>Nasopharyngeal carcinoma (NPC) is a clinically aggressive malignancy in which epithelial-mesenchymal transition (EMT) plays a central role in invasion, metastasis, and therapeutic resistance. However, the coordinated transcriptional organization, regulatory mechanisms, and functional relevance of EMT-associated genes in NPC remain insufficiently defined. This study aimed to identify EMT-related hub genes in NPC and integrate multiomics and functional evidence to elucidate their biological and clinical significance. Weighted gene coexpression network analysis was performed on the GSE12452 dataset to identify EMT-associated modules and hub genes. Multiomics validation, including transcriptomic, protein level, methylation, mutation, CNV, survival, and drug response profiling, was conducted using GSCA, HPA, OncoDB, cBioPortal, and GDC databases. miRNA regulators were predicted using TargetScan and validated by dual-luciferase assays. Functional significance was assessed through RT-qPCR, Western blotting, apoptosis, viability, colony formation, and wound healing assays following treatment of NPC cells with afatinib or SB431542. WGCNA identified four EMT hub genes, VIM, SNAI1, ZEB1, and FN1, which were consistently overexpressed in NPC. These genes were hypomethylated, exhibited CNV alterations, and were associated with poor survival and broad drug resistance profiles. Predicted miRNA interactions were experimentally validated. Pharmacologic inhibition of EMT-associated signaling significantly reduced hub gene expression and suppressed malignant phenotypes across multiple NPC cell lines. This integrative analysis identifies VIM, SNAI1, ZEB1, and FN1 as a candidate EMT-associated hub signature linked with NPC progression, prognosis, and drug response patterns. Pharmacological inhibition of EMT-associated signaling reduced hub gene expression and suppressed malignant cellular phenotypes, suggesting that this EMT hub network may have potential value as a prognostic biomarker panel and as a putative therapeutic vulnerability requiring further validation.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"21589-21610"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}