{"title":"aloin介导的STAT3/SLC7A11信号在头颈部鳞状细胞癌中的调控机制","authors":"Li-Jian Wang, Jun Wang","doi":"10.1007/s10616-025-00798-4","DOIUrl":null,"url":null,"abstract":"<p><p>This study aims to investigate the mechanisms by which Aloin (AloAB) mediates the signal transducer and activator of transcription 3 (STAT3)/solute carrier family 7 member 11 (SLC7A11) signaling pathway in head and neck squamous cell carcinoma (HNSCC). HNSCC cells were treated with 50-1000 μM AloAB to assess dose-dependent cytotoxicity and its effects on the STAT3/SLC7A11 pathway. CRISPR activation plasmids were used to overexpress STAT3 or SLC7A11 in FaDu cells. Subsequent analyses included migration and invasion assays, lipid peroxidation (LPO) assay, intracellular iron assay, as well as the measurement of oxidative stress markers and ferroptosis-related factors. Epithelial-mesenchymal transition (EMT) markers and matrix metalloproteinase (MMP) expression levels were also assessed. AloAB treatment significantly reduced cell viability in HNSCC cells at higher concentrations. It inhibited FaDu cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while downregulating STAT3/SLC7A11 expression. Additionally, AloAB induced oxidative stress and ferroptosis, as indicated by elevated malondialdehyde (MDA), Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4), lipid peroxidation (LPO), and iron levels, alongside decreased levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase 4 (GPX4), reduced glutathione (GSH), and glutathione peroxidase (GPx). Overexpression of STAT3 or SLC7A11 reversed these effects, restoring oxidative stress markers and ferroptosis-related factors to control levels. Moreover, the suppression of EMT was alleviated by the upregulation of E-cadherin and the downregulation of N-cadherin, Vimentin, MMP2, and MMP9. AloAB exerts anti-tumor effects on HNSCC cells by inhibiting the STAT3/SLC7A11 signaling pathway, inducing oxidative stress, ferroptosis, and suppression of migration, invasion, and EMT.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s10616-025-00798-4.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"77 4","pages":"137"},"PeriodicalIF":2.0000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229470/pdf/","citationCount":"0","resultStr":"{\"title\":\"Mechanistic insights into Aloin-mediated regulation of STAT3/SLC7A11 signaling in head and neck squamous cell carcinoma.\",\"authors\":\"Li-Jian Wang, Jun Wang\",\"doi\":\"10.1007/s10616-025-00798-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>This study aims to investigate the mechanisms by which Aloin (AloAB) mediates the signal transducer and activator of transcription 3 (STAT3)/solute carrier family 7 member 11 (SLC7A11) signaling pathway in head and neck squamous cell carcinoma (HNSCC). HNSCC cells were treated with 50-1000 μM AloAB to assess dose-dependent cytotoxicity and its effects on the STAT3/SLC7A11 pathway. CRISPR activation plasmids were used to overexpress STAT3 or SLC7A11 in FaDu cells. Subsequent analyses included migration and invasion assays, lipid peroxidation (LPO) assay, intracellular iron assay, as well as the measurement of oxidative stress markers and ferroptosis-related factors. Epithelial-mesenchymal transition (EMT) markers and matrix metalloproteinase (MMP) expression levels were also assessed. AloAB treatment significantly reduced cell viability in HNSCC cells at higher concentrations. It inhibited FaDu cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while downregulating STAT3/SLC7A11 expression. Additionally, AloAB induced oxidative stress and ferroptosis, as indicated by elevated malondialdehyde (MDA), Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4), lipid peroxidation (LPO), and iron levels, alongside decreased levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase 4 (GPX4), reduced glutathione (GSH), and glutathione peroxidase (GPx). Overexpression of STAT3 or SLC7A11 reversed these effects, restoring oxidative stress markers and ferroptosis-related factors to control levels. Moreover, the suppression of EMT was alleviated by the upregulation of E-cadherin and the downregulation of N-cadherin, Vimentin, MMP2, and MMP9. AloAB exerts anti-tumor effects on HNSCC cells by inhibiting the STAT3/SLC7A11 signaling pathway, inducing oxidative stress, ferroptosis, and suppression of migration, invasion, and EMT.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s10616-025-00798-4.</p>\",\"PeriodicalId\":10890,\"journal\":{\"name\":\"Cytotechnology\",\"volume\":\"77 4\",\"pages\":\"137\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2025-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229470/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cytotechnology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s10616-025-00798-4\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/7/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cytotechnology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s10616-025-00798-4","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/3 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Mechanistic insights into Aloin-mediated regulation of STAT3/SLC7A11 signaling in head and neck squamous cell carcinoma.
This study aims to investigate the mechanisms by which Aloin (AloAB) mediates the signal transducer and activator of transcription 3 (STAT3)/solute carrier family 7 member 11 (SLC7A11) signaling pathway in head and neck squamous cell carcinoma (HNSCC). HNSCC cells were treated with 50-1000 μM AloAB to assess dose-dependent cytotoxicity and its effects on the STAT3/SLC7A11 pathway. CRISPR activation plasmids were used to overexpress STAT3 or SLC7A11 in FaDu cells. Subsequent analyses included migration and invasion assays, lipid peroxidation (LPO) assay, intracellular iron assay, as well as the measurement of oxidative stress markers and ferroptosis-related factors. Epithelial-mesenchymal transition (EMT) markers and matrix metalloproteinase (MMP) expression levels were also assessed. AloAB treatment significantly reduced cell viability in HNSCC cells at higher concentrations. It inhibited FaDu cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while downregulating STAT3/SLC7A11 expression. Additionally, AloAB induced oxidative stress and ferroptosis, as indicated by elevated malondialdehyde (MDA), Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4), lipid peroxidation (LPO), and iron levels, alongside decreased levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase 4 (GPX4), reduced glutathione (GSH), and glutathione peroxidase (GPx). Overexpression of STAT3 or SLC7A11 reversed these effects, restoring oxidative stress markers and ferroptosis-related factors to control levels. Moreover, the suppression of EMT was alleviated by the upregulation of E-cadherin and the downregulation of N-cadherin, Vimentin, MMP2, and MMP9. AloAB exerts anti-tumor effects on HNSCC cells by inhibiting the STAT3/SLC7A11 signaling pathway, inducing oxidative stress, ferroptosis, and suppression of migration, invasion, and EMT.
Supplementary information: The online version contains supplementary material available at 10.1007/s10616-025-00798-4.
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The scope of the Journal includes:
1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products.
2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools.
3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research.
4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy.
5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.
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