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.
**背景/目的：** 慢性炎症是癌症发生的关键驱动因素。白细胞介素33（IL-33）已成为参与易癌性慢性炎症发病机制的关键因子。IL-33通过其细胞因子与核蛋白的双重功能，启动慢性炎症及癌症进程。然而，能够通过抑制IL-33表达以阻断其细胞因子及核功能的小分子药物尚未得到充分探索。 **方法：** 本研究探讨了托烷司琼对IL-33表达的影响及其在抑制胰腺炎及胰腺炎介导的胰腺癌中的作用。 **结果：** 我们发现托烷司琼可显著抑制IL-33表达，具有作为预防慢性炎症及其癌症后遗症的新型治疗策略的潜力。通过对1018种美国食品药品监督管理局（FDA）已批准药物进行筛选，我们发现托烷司琼——一种常用于防治恶心呕吐的5-羟色胺3型（5-HT3）受体拮抗剂——能通过抑制IRF3活化有效阻断IL-33表达。在动物实验中，托烷司琼可抑制小鼠胰腺炎及其向胰腺癌的进展。 **结论：** 托烷司琼是一种IL-33抑制剂，可为预防和治疗慢性胰腺炎及其相关癌症提供新型治疗策略。
肿瘤(癌症)患者之家