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Melatonin reverses nasopharyngeal carcinoma cisplatin chemoresistance by inhibiting the Wnt/β-catenin signaling pathway
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 melat...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138577/ https://www.ncbi.nlm.nih.gov/pubmed/32203052 http://dx.doi.org/10.18632/aging.102968 |
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author | Zhang, Jian Xie, Tao Zhong, Xi Jiang, Hua-Li Li, Rong Wang, Bai-Yao Huang, Xiao-Ting Cen, Bo-Hong Yuan, Ya-Wei |
author_facet | Zhang, Jian Xie, Tao Zhong, Xi Jiang, Hua-Li Li, Rong Wang, Bai-Yao Huang, Xiao-Ting Cen, Bo-Hong Yuan, Ya-Wei |
author_sort | Zhang, Jian |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7138577 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-71385772020-04-13 Melatonin reverses nasopharyngeal carcinoma cisplatin chemoresistance by inhibiting the Wnt/β-catenin signaling pathway Zhang, Jian Xie, Tao Zhong, Xi Jiang, Hua-Li Li, Rong Wang, Bai-Yao Huang, Xiao-Ting Cen, Bo-Hong Yuan, Ya-Wei Aging (Albany NY) Research Paper 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. Impact Journals 2020-03-23 /pmc/articles/PMC7138577/ /pubmed/32203052 http://dx.doi.org/10.18632/aging.102968 Text en Copyright © 2020 Zhang et al. http://creativecommons.org/licenses/by/3.0/ 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. |
spellingShingle | Research Paper Zhang, Jian Xie, Tao Zhong, Xi Jiang, Hua-Li Li, Rong Wang, Bai-Yao Huang, Xiao-Ting Cen, Bo-Hong Yuan, Ya-Wei Melatonin reverses nasopharyngeal carcinoma cisplatin chemoresistance by inhibiting the Wnt/β-catenin signaling pathway |
title | Melatonin reverses nasopharyngeal carcinoma cisplatin chemoresistance by inhibiting the Wnt/β-catenin signaling pathway |
title_full | Melatonin reverses nasopharyngeal carcinoma cisplatin chemoresistance by inhibiting the Wnt/β-catenin signaling pathway |
title_fullStr | Melatonin reverses nasopharyngeal carcinoma cisplatin chemoresistance by inhibiting the Wnt/β-catenin signaling pathway |
title_full_unstemmed | Melatonin reverses nasopharyngeal carcinoma cisplatin chemoresistance by inhibiting the Wnt/β-catenin signaling pathway |
title_short | Melatonin reverses nasopharyngeal carcinoma cisplatin chemoresistance by inhibiting the Wnt/β-catenin signaling pathway |
title_sort | melatonin reverses nasopharyngeal carcinoma cisplatin chemoresistance by inhibiting the wnt/β-catenin signaling pathway |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138577/ https://www.ncbi.nlm.nih.gov/pubmed/32203052 http://dx.doi.org/10.18632/aging.102968 |
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