{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T01:21:57Z","timestamp":1793409717104,"version":"4.5.0"},"reference-count":61,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,22]],"date-time":"2025-06-22T00:00:00Z","timestamp":1750550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2024-00406114"],"award-info":[{"award-number":["RS-2024-00406114"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["R01CA283214"],"award-info":[{"award-number":["R01CA283214"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Burroughs Wellcome Fund","award":["RS-2024-00406114"],"award-info":[{"award-number":["RS-2024-00406114"]}]},{"name":"Burroughs Wellcome Fund","award":["R01CA283214"],"award-info":[{"award-number":["R01CA283214"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Chronic inflammation is a key driver of cancer. Interleukin 33 (IL-33) has emerged as a crucial factor involved in the pathogenesis of cancer-prone chronic inflammation. IL-33 functions as a cytokine and a nuclear protein to initiate chronic inflammation and cancer. However, small molecules capable of suppressing IL-33 expression to block its cytokine and nuclear functions are underexplored. Methods: The impact of tropisetron on IL-33 expression and its role in suppressing pancreatitis and pancreatitis-mediated pancreatic cancer were examined. Results: We demonstrate that tropisetron suppresses IL-33 expression, with high potential to serve as a novel therapeutic strategy for preventing chronic inflammation and its cancer sequela. Through screening 1018 Food and Drug Administration (FDA)-approved drugs, we discovered that tropisetron, a 5-hydroxytryptamine type 3 (5-HT3) antagonist commonly used to prevent and treat nausea and vomiting, effectively blocked IL-33 expression by suppressing IRF3 activation. Tropisetron inhibited pancreatitis and its progression to pancreatic cancer in mice. Conclusions: Tropisetron is an IL-33 inhibitor and can provide a novel therapeutic strategy to prevent and treat chronic pancreatitis and its associated cancer.<\/jats:p>","DOI":"10.3390\/cancers17132087","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T03:39:26Z","timestamp":1750649966000},"page":"2087","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Tropisetron Suppresses Chronic Pancreatitis and Pancreatic Cancer by Blocking Interleukin 33 Expression"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2175-9679","authenticated-orcid":false,"given":"An-Na","family":"Bae","sequence":"first","affiliation":[{"name":"Department of Anatomy, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8503-9806","authenticated-orcid":false,"given":"Mahsa","family":"Mortaja","sequence":"additional","affiliation":[{"name":"Center for Cancer Immunology, Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"},{"name":"Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YeePui","family":"Yeung","sequence":"additional","affiliation":[{"name":"Center for Cancer Immunology, Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"},{"name":"Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6275-0451","authenticated-orcid":false,"given":"Jiao","family":"Huang","sequence":"additional","affiliation":[{"name":"Center for Cancer Immunology, Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"},{"name":"Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0488-7791","authenticated-orcid":false,"given":"Jong Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"},{"name":"Center for Cancer Immunology, Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"},{"name":"Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7913-2641","authenticated-orcid":false,"given":"Shadmehr","family":"Demehri","sequence":"additional","affiliation":[{"name":"Center for Cancer Immunology, Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"},{"name":"Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/s41392-021-00658-5","article-title":"Inflammation and tumor progression: Signaling pathways and targeted intervention","volume":"6","author":"Zhao","year":"2021","journal-title":"Signal Transduct. 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