褪黑激素的功效及其在人类膀胱癌中的生物学意义仍知之甚少。本研究旨在探讨褪黑激素在尿路上皮癌发生中的功能作用。在暴露于化学致癌剂 3-甲基胆蒽的人类正常尿路上皮 SVHUC 细胞中，我们评估了褪黑激素对肿瘤/恶性转化的影响。在具有致癌物质的体外系统中挑战中，褪黑素显着阻止了 SV-HUC-1 细胞的肿瘤转化。此外，褪黑素处理导致 SV-HUC-1 细胞中 SIRT1、Rb1 和 E-cadherin 的表达增加，而 N-cadherin 和 FGFR3 的表达减少。此外，GSE3167的公开数据集显示，与邻近的正常尿路上皮组织相比，褪黑激素受体1和褪黑激素受体2的表达在膀胱尿路上皮癌组织中显着下调。这些发现表明，褪黑激素可作为尿路上皮肿瘤发生的抑制剂。据我们所知，这是第一个证明褪黑激素对尿路上皮癌发展影响的临床前研究。版权所有 © 2024，国际抗癌研究所（George J. Delinasios 博士），保留所有权利。

The efficacy of melatonin and its biological significance in human bladder cancer remain poorly understood. This study aimed to investigate the functional role of melatonin in urothelial carcinogenesis.In human normal urothelial SVHUC cells with exposure to the chemical carcinogen 3-methylcholanthrene, we assessed the effects of melatonin on the neoplastic/malignant transformation.In the in vitro system with carcinogen challenge, melatonin significantly prevented the neoplastic transformation of SV-HUC-1 cells. In addition, melatonin treatment resulted in increased expression of SIRT1, Rb1, and E-cadherin, and decreased expression of N-cadherin and FGFR3 in SV-HUC-1 cells. Furthermore, publicly available datasets from GSE3167 revealed that the expression of melatonin receptor 1 and melatonin receptor 2 was significantly down-regulated in bladder urothelial carcinoma tissues, compared with adjacent normal urothelial tissues.These findings indicate that melatonin serves as a suppressor for urothelial tumorigenesis. To the best of our knowledge, this is the first preclinical study demonstrating the impact of melatonin on the development of urothelial cancer.Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.