{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:54:21Z","timestamp":1790916861991,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research","award":["PRIN 2017XJ38A4"],"award-info":[{"award-number":["PRIN 2017XJ38A4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gastric cancer (GC) continues to be a major cause of cancer-related deaths globally, primarily due to resistance to standard treatments like 5-fluorouracil (5FU). The transforming growth factor-\u03b2 (TGF-\u03b2) signaling pathway is recognized as a key contributor to tumor progression and resistance to therapy. This work investigated the therapeutic potential of targeting TGF-\u03b2 receptor I (TGFBR1) with the selective inhibitor SB431542 to enhance the effect of 5FU in GC. Analysis of public gene expression datasets revealed that increased levels of TGF-\u03b2 and TGFBR1 are significantly connected with poor prognosis, particularly in high-grade GC. In vitro experiments using AGS and SNU-1 cell lines demonstrated that co-treatment with SB431542 and 5FU significantly reduced cell viability, making GC cells more sensitive to 5FU. This combination treatment led to a significant activation of caspase-dependent apoptosis, indicating an enhanced pro-apoptotic effect. These findings suggest that TGFBR1 inhibition could provide a strategic approach to reduce the dosage of 5FU, thereby minimizing its severe side effects in gastric cancer patients. Furthermore, these results underscore the potential of TGFBR1 as both a prognostic biomarker and a therapeutic target, warranting further investigation in aggressive forms of gastric cancer.<\/jats:p>","DOI":"10.3390\/ijms262311250","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T09:50:26Z","timestamp":1763718626000},"page":"11250","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["TGF-\u03b2 Receptor Inhibitor SB431542 Enhanced the Sensitivity of Gastric Cancer to 5-Fluorouracil: New Combined Targeted Therapy"],"prefix":"10.3390","volume":"26","author":[{"given":"Sara","family":"Bonomo","sequence":"first","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7706-0672","authenticated-orcid":false,"given":"Roberto","family":"Giovannoni","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, Via Derna 1, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4852-1318","authenticated-orcid":false,"given":"Marialuisa","family":"Lavitrano","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0899-7613","authenticated-orcid":false,"given":"Massimiliano","family":"Cadamuro","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5665-9558","authenticated-orcid":false,"given":"Donatella","family":"Conconi","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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