Targeted inhibition of the PTEN/PI3K/AKT pathway by YSV induces cell cycle arrest and apoptosis in oral squamous cell carcinoma
Abstract Background Tyroservatide (YSV), a bioactive tripeptide, holds potential as an anti-tumor agent. However, its specific effects on oral squamous cell carcinoma (OSCC) have not been elucidated. This study aims to investigate the inhibitory effects of YSV on OSCC and explore the underlying mole...
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BMC
2025-02-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06169-z |
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| author | Lin Qiu Qian Gao Yiheng Liao Xinxin Li Cuiying Li |
| author_facet | Lin Qiu Qian Gao Yiheng Liao Xinxin Li Cuiying Li |
| author_sort | Lin Qiu |
| collection | DOAJ |
| description | Abstract Background Tyroservatide (YSV), a bioactive tripeptide, holds potential as an anti-tumor agent. However, its specific effects on oral squamous cell carcinoma (OSCC) have not been elucidated. This study aims to investigate the inhibitory effects of YSV on OSCC and explore the underlying molecular mechanisms. Methods A series of in vitro experiments were conducted to assess the impact of YSV on OSCC cell viability, colony formation, cell cycle, and apoptosis. RNA sequencing (RNA-seq), molecular docking, and western blotting were employed to investigate the molecular mechanisms. Additionally, a subcutaneous tumor model was established to validate the in vitro findings. Furthermore, PI3K inhibitors LY294002 and PI3K-IN-1, were used to confirm the role of the PTEN/PI3K/AKT pathway in YSV-mediated OSCC inhibition. Cell cycle and apoptosis were analyzed to assess the combined effect of YSV and LY294002. Results YSV significantly inhibited OSCC proliferation by inducing cell cycle arrest and apoptosis. RNA-seq and molecular docking revealed that YSV regulated the PTEN/PI3K/AKT signaling pathway. Western blotting confirmed the modulation of this pathway both in vitro and in vivo. The use of PI3K inhibitors, LY294002 and PI3K-IN-1, further validated the involvement of the PTEN/PI3K/AKT pathway in YSV-induced anti-tumor effects. Notably, the combination of YSV and LY294002 synergistically enhanced cell cycle arrest and apoptosis, demonstrating effective anti-tumor activity. In vivo experiments also supported these findings. Conclusion YSV inhibited the progression of OSCC by promoting cell cycle arrest and apoptosis through the regulation of the PTEN/PI3K/AKT signaling pathway. The combination of YSV and PI3K inhibitors, such as LY294002, exhibited enhanced anti-tumor activity, suggesting potential therapeutic strategies for OSCC treatment. Graphical abstract |
| format | Article |
| id | doaj-art-870e4a6a07054f4887c0059595f19481 |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-870e4a6a07054f4887c0059595f194812025-02-09T12:52:24ZengBMCJournal of Translational Medicine1479-58762025-02-0123111710.1186/s12967-025-06169-zTargeted inhibition of the PTEN/PI3K/AKT pathway by YSV induces cell cycle arrest and apoptosis in oral squamous cell carcinomaLin Qiu0Qian Gao1Yiheng Liao2Xinxin Li3Cuiying Li4Central Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesCentral Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesCentral Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesNational Key Laboratory of Efficacy and Mechanism on Chinese Medicine for Metabolic Diseases, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese MedicineCentral Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesAbstract Background Tyroservatide (YSV), a bioactive tripeptide, holds potential as an anti-tumor agent. However, its specific effects on oral squamous cell carcinoma (OSCC) have not been elucidated. This study aims to investigate the inhibitory effects of YSV on OSCC and explore the underlying molecular mechanisms. Methods A series of in vitro experiments were conducted to assess the impact of YSV on OSCC cell viability, colony formation, cell cycle, and apoptosis. RNA sequencing (RNA-seq), molecular docking, and western blotting were employed to investigate the molecular mechanisms. Additionally, a subcutaneous tumor model was established to validate the in vitro findings. Furthermore, PI3K inhibitors LY294002 and PI3K-IN-1, were used to confirm the role of the PTEN/PI3K/AKT pathway in YSV-mediated OSCC inhibition. Cell cycle and apoptosis were analyzed to assess the combined effect of YSV and LY294002. Results YSV significantly inhibited OSCC proliferation by inducing cell cycle arrest and apoptosis. RNA-seq and molecular docking revealed that YSV regulated the PTEN/PI3K/AKT signaling pathway. Western blotting confirmed the modulation of this pathway both in vitro and in vivo. The use of PI3K inhibitors, LY294002 and PI3K-IN-1, further validated the involvement of the PTEN/PI3K/AKT pathway in YSV-induced anti-tumor effects. Notably, the combination of YSV and LY294002 synergistically enhanced cell cycle arrest and apoptosis, demonstrating effective anti-tumor activity. In vivo experiments also supported these findings. Conclusion YSV inhibited the progression of OSCC by promoting cell cycle arrest and apoptosis through the regulation of the PTEN/PI3K/AKT signaling pathway. The combination of YSV and PI3K inhibitors, such as LY294002, exhibited enhanced anti-tumor activity, suggesting potential therapeutic strategies for OSCC treatment. Graphical abstracthttps://doi.org/10.1186/s12967-025-06169-zOral squamous cell carcinomaTyroservatideProliferationCell cycleApoptosisPTEN/PI3K/AKT signaling pathway |
| spellingShingle | Lin Qiu Qian Gao Yiheng Liao Xinxin Li Cuiying Li Targeted inhibition of the PTEN/PI3K/AKT pathway by YSV induces cell cycle arrest and apoptosis in oral squamous cell carcinoma Journal of Translational Medicine Oral squamous cell carcinoma Tyroservatide Proliferation Cell cycle Apoptosis PTEN/PI3K/AKT signaling pathway |
| title | Targeted inhibition of the PTEN/PI3K/AKT pathway by YSV induces cell cycle arrest and apoptosis in oral squamous cell carcinoma |
| title_full | Targeted inhibition of the PTEN/PI3K/AKT pathway by YSV induces cell cycle arrest and apoptosis in oral squamous cell carcinoma |
| title_fullStr | Targeted inhibition of the PTEN/PI3K/AKT pathway by YSV induces cell cycle arrest and apoptosis in oral squamous cell carcinoma |
| title_full_unstemmed | Targeted inhibition of the PTEN/PI3K/AKT pathway by YSV induces cell cycle arrest and apoptosis in oral squamous cell carcinoma |
| title_short | Targeted inhibition of the PTEN/PI3K/AKT pathway by YSV induces cell cycle arrest and apoptosis in oral squamous cell carcinoma |
| title_sort | targeted inhibition of the pten pi3k akt pathway by ysv induces cell cycle arrest and apoptosis in oral squamous cell carcinoma |
| topic | Oral squamous cell carcinoma Tyroservatide Proliferation Cell cycle Apoptosis PTEN/PI3K/AKT signaling pathway |
| url | https://doi.org/10.1186/s12967-025-06169-z |
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