骨转移是晚期前列腺癌（PCa）患者死亡的主要原因。 PCa倾向于扩散到骨骼并获得骨样表型，引起成骨细胞骨转移。不幸的是，这种情况没有有效的治疗方法。然而，调节昼夜节律的褪黑激素被发现具有抗肿瘤特性。目前尚未确定其是否能有效治疗成骨性 PCa 转移。我们的研究结果表明，褪黑激素抑制成骨细胞 PCa 细胞中内皮素-1 (ET-1) 的产生，从而抑制成骨细胞分化。临床结果表明，与非转移性前列腺癌患者相比，骨转移性前列腺癌患者的 ET-1 水平较高。此外，褪黑素诱导的 miR-let-7f-5p 抑制 ET-1 促进的成骨细胞 PCa 中的成骨细胞分化。褪黑素还抑制成骨细胞 PCa 的拟骨特性。重要的是，在胫骨内注射 PCa 转移模型中，褪黑激素减少了成骨细胞 PCa 肿瘤的生长，抑制体内 ET-1 的产生和成骨细胞分化。总而言之，褪黑激素通过上调 miR-let-7f-5p 减少 ET-1 的产生来抑制成骨细胞 PCa 调节的成骨细胞生成，同时抑制成骨细胞 PCa 中的拟骨特性。褪黑素疗法可能是治疗成骨性 PCa 骨转移的一种有前景的方法。© 2024 John Wiley

Bone metastasis is the primary cause of death among patients with advanced prostate cancer (PCa). PCa tends to spread to bones and acquire the bone-like phenotype, causing osteoblastic bone metastasis. Unfortunately, there is no effective treatment for this condition. However, melatonin, which regulates our circadian rhythm, has been found to have anti-tumor properties. It has yet to be established whether it is effective in treating osteoblastic PCa metastasis. Our findings show that melatonin inhibits the production of endothelin-1 (ET-1) in osteoblastic PCa cells, suppressing osteoblast differentiation. Clinical results indicate that bone metastatic PCa patients have higher levels of ET-1 compared to nonmetastatic PCa patients. Furthermore, melatonin-induced miR-let-7f-5p inhibits ET-1-promoted osteoblast differentiation in osteoblastic PCa. Melatonin also suppresses the property of osteomimicry in osteoblastic PCa cells. Importantly, in the intratibia injection PCa metastasis model, melatonin decreased osteoblastic PCa tumor growth, inhibiting ET-1 production and osteoblast differentiation in vivo. Taken together, melatonin inhibits osteoblastic PCa-regulated osteoblastogenesis by reducing ET-1 production through upregulation of miR-let-7f-5p, while suppressing the property of osteomimicry in osteoblastic PCa. Melatonin therapy could be a promising approach to treating bone metastasis in osteoblastic PCa.© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.