Department of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, P. R. China.
Department of Radiology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, P. R. China.
Aging (Albany NY). 2020 Mar 23;12(6):5423-5438. doi: 10.18632/aging.102968.
Cisplatin (DDP)-based concurrent chemo-radiotherapy is a standard approach to treat locoregionally advanced nasopharyngeal carcinoma (NPC). However, many patients eventually develop recurrence and/or distant metastasis due to chemoresistance. In this study, we aimed to elucidate the effects of melatonin on DDP chemoresistance in NPC cell lines in and , and we explored potential chemoresistance mechanisms. We found that DDP chemoresistance in NPC cells is mediated through the Wnt/β-catenin signaling pathway. Melatonin not only reversed DDP chemoresistance, but also enhanced DDP antitumor activity by suppressing the nuclear translocation of β-catenin, and reducing expression of Wnt/β-catenin response genes in NPC cells. In , combined treatment with DDP and melatonin reduced tumor burden to a greater extent than single drug-treatments in an orthotopic xenograft mouse model. Our findings provide novel evidence that melatonin inhibits the Wnt/β-catenin pathway in NPC, and suggest that melatonin could be applied in combination with DDP to treat NPC.
顺铂（DDP）为基础的同期放化疗是治疗局部晚期鼻咽癌（NPC）的标准方法。然而，由于化疗耐药性，许多患者最终会出现复发和/或远处转移。在这项研究中，我们旨在阐明褪黑素对 NPC 细胞系中 DDP 耐药性的影响，并探讨潜在的耐药机制。我们发现 DDP 耐药性是通过 Wnt/β-catenin 信号通路介导的。褪黑素不仅逆转了 DDP 耐药性，还通过抑制 β-catenin 的核易位和降低 NPC 细胞中 Wnt/β-catenin 反应基因的表达来增强 DDP 的抗肿瘤活性。在体内，与单独用药相比，DDP 和褪黑素联合治疗在 NPC 的原位移植瘤小鼠模型中更能显著降低肿瘤负担。我们的研究结果为褪黑素抑制 NPC 中的 Wnt/β-catenin 通路提供了新的证据，并提示褪黑素可与 DDP 联合应用于 NPC 的治疗。
