Research Paper Volume 12, Issue 6 pp 5423—5438

Melatonin reverses nasopharyngeal carcinoma cisplatin chemoresistance by inhibiting the Wnt/β-catenin signaling pathway

Jian Zhang 1, *, , Tao Xie 1, *, , Xi Zhong 2, *, , Hua-Li Jiang 3, *, , Rong Li 1, , Bai-Yao Wang 1, , Xiao-Ting Huang 1, , Bo-Hong Cen 1, , Ya-Wei Yuan 1, ,

  • 1 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
  • 2 Department of Radiology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, P. R. China
  • 3 Department of Cardiovascularology, Tungwah Hospital of Sun Yat-Sen University, Dongguan, P.R. China
* Equal contribution

received: December 1, 2019 ; accepted: March 16, 2020 ; published: March 23, 2020 ;

https://doi.org/10.18632/aging.102968
How to Cite

Copyright © 2020 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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 vitro and vivo, 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 vivo, 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.

Abbreviations

NPC: Nasopharyngeal carcinoma; DDP: Cisplatin; LA-NPC: locoregionally advanced nasopharyngeal carcinoma; DEGs: Differentially expressed genes; GSEA: Gene set enrichment analysis; IHC: Immunohistochemistry; DMFS: distant metastasis-free survival.