{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:04:47Z","timestamp":1792789487284,"version":"4.5.0"},"reference-count":46,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea government","award":["NRF-2017R1C1B5017365"],"award-info":[{"award-number":["NRF-2017R1C1B5017365"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Serotonin or 5-hydroxytryptamine (5-HT) has been implicated in promoting cancer cell growth by acting on 5-HT receptors, such as 5-HT1 and 5-HT2 receptors. However, the role of 5-HT3 receptor antagonists in gastric cancer cell lines remains unclear. This study aimed to evaluate the effect of 5-HT3 receptor antagonists (ondansetron, palonosetron, and ramosetron) on cancer cell growth using AGS and MKN-1 cell lines, as well as the xenograft mouse model. All the three antagonists inhibited cell proliferation, migration, and colony formation in AGS cells. Specifically, palonosetron induced G1 cell cycle arrest, autophagy, and phosphorylation of GSK3\u03b2, along with increased expression of p27, p53, and LC3B. In vivo studies demonstrated that palonosetron reduced tumor growth and modulated pro-inflammatory cytokines\u2014tumor necrosis factor alpha, interleukin 6, and interleukin 1\u03b2. These findings suggest that 5-HT3 receptor antagonists, especially palonosetron, exert anti-tumor effects in gastric cancer through G1 cell cycle regulation and immunomodulation. The results position palonosetron as a promising lead for further preclinical development in gastric cancer.<\/jats:p>","DOI":"10.3390\/ijms262010039","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T14:04:02Z","timestamp":1760537042000},"page":"10039","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Palonosetron, a 5-HT3 Receptor Antagonist, Induces G1 Cell Cycle Arrest and Autophagy in Gastric Cancer Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6334-7541","authenticated-orcid":false,"given":"Young Chul","family":"Yoo","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4904-3154","authenticated-orcid":false,"given":"Lin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihak","family":"Lee","sequence":"additional","affiliation":[{"name":"Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeeun Rachel","family":"Shin","sequence":"additional","affiliation":[{"name":"Sha Tin College, No. 3 Lai Wo Lane, Fo Tan, Sha Tin, New Territories, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju Eun","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3685-2005","authenticated-orcid":false,"given":"Na Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s12079-018-0482-2","article-title":"The 5-Hydroxytryptamine signaling map: An overview of serotonin-serotonin receptor mediated signaling network","volume":"12","author":"Sahu","year":"2018","journal-title":"J. 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