IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma

BACKGROUND: In promoting tumour malignancy IL-6 signalling is considered to have an important role. However, the biological roles of IL-6 on radiosensitivity in oral squamous cell carcinoma (OSCC) remain largely unclear. The objective of this study is to determine the effects and molecular mechanism...

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Autores principales: Matsuoka, Yuichiro, Nakayama, Hideki, Yoshida, Ryoji, Hirosue, Akiyuki, Nagata, Masashi, Tanaka, Takuya, Kawahara, Kenta, Sakata, Junki, Arita, Hidetaka, Nakashima, Hikaru, Shinriki, Satoru, Fukuma, Daiki, Ogi, Hidenao, Hiraki, Akimitsu, Shinohara, Masanori, Toya, Ryo, Murakami, Ryuji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104896/
https://www.ncbi.nlm.nih.gov/pubmed/27736845
http://dx.doi.org/10.1038/bjc.2016.327
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author Matsuoka, Yuichiro
Nakayama, Hideki
Yoshida, Ryoji
Hirosue, Akiyuki
Nagata, Masashi
Tanaka, Takuya
Kawahara, Kenta
Sakata, Junki
Arita, Hidetaka
Nakashima, Hikaru
Shinriki, Satoru
Fukuma, Daiki
Ogi, Hidenao
Hiraki, Akimitsu
Shinohara, Masanori
Toya, Ryo
Murakami, Ryuji
author_facet Matsuoka, Yuichiro
Nakayama, Hideki
Yoshida, Ryoji
Hirosue, Akiyuki
Nagata, Masashi
Tanaka, Takuya
Kawahara, Kenta
Sakata, Junki
Arita, Hidetaka
Nakashima, Hikaru
Shinriki, Satoru
Fukuma, Daiki
Ogi, Hidenao
Hiraki, Akimitsu
Shinohara, Masanori
Toya, Ryo
Murakami, Ryuji
author_sort Matsuoka, Yuichiro
collection PubMed
description BACKGROUND: In promoting tumour malignancy IL-6 signalling is considered to have an important role. However, the biological roles of IL-6 on radiosensitivity in oral squamous cell carcinoma (OSCC) remain largely unclear. The objective of this study is to determine the effects and molecular mechanisms of IL-6 on radiosensitivity in OSCC. METHODS: Two OSCC cell lines, and OSCC tissue samples with radioresistant cells were used. We examined the effects of IL-6, or tocilizumab, a humanised anti-human IL-6 receptor antibody, or both on radiosensitivity and DNA damage after X-ray irradiation in vitro. In addition, we investigated the involvement of the Nrf2-antioxidant pathway in IL-6-mediated radioresistant mechanisms using OSCC cell lines and tissues. RESULTS: Increased levels of IL-6 suppressed radiation-induced cell death, and the blockade of IL-6 signalling by tocilizumab sensitised tumour cells to radiation. The radioresistant effect of IL-6 was associated with decreased DNA damage after radiation. We also found that IL-6 promotes the activation of not only the downstream molecule STAT3 but also the Nrf2-antioxidant pathway, leading to a significant decrease in oxidative stress by upregulating Mn-SOD. CONCLUSIONS: These results indicate that the blockade of IL-6 signalling combined with conventional radiotherapy could augment the treatment response and survival rate in patients with radioresistant OSCC.
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spelling pubmed-51048962017-11-08 IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma Matsuoka, Yuichiro Nakayama, Hideki Yoshida, Ryoji Hirosue, Akiyuki Nagata, Masashi Tanaka, Takuya Kawahara, Kenta Sakata, Junki Arita, Hidetaka Nakashima, Hikaru Shinriki, Satoru Fukuma, Daiki Ogi, Hidenao Hiraki, Akimitsu Shinohara, Masanori Toya, Ryo Murakami, Ryuji Br J Cancer Translational Therapeutics BACKGROUND: In promoting tumour malignancy IL-6 signalling is considered to have an important role. However, the biological roles of IL-6 on radiosensitivity in oral squamous cell carcinoma (OSCC) remain largely unclear. The objective of this study is to determine the effects and molecular mechanisms of IL-6 on radiosensitivity in OSCC. METHODS: Two OSCC cell lines, and OSCC tissue samples with radioresistant cells were used. We examined the effects of IL-6, or tocilizumab, a humanised anti-human IL-6 receptor antibody, or both on radiosensitivity and DNA damage after X-ray irradiation in vitro. In addition, we investigated the involvement of the Nrf2-antioxidant pathway in IL-6-mediated radioresistant mechanisms using OSCC cell lines and tissues. RESULTS: Increased levels of IL-6 suppressed radiation-induced cell death, and the blockade of IL-6 signalling by tocilizumab sensitised tumour cells to radiation. The radioresistant effect of IL-6 was associated with decreased DNA damage after radiation. We also found that IL-6 promotes the activation of not only the downstream molecule STAT3 but also the Nrf2-antioxidant pathway, leading to a significant decrease in oxidative stress by upregulating Mn-SOD. CONCLUSIONS: These results indicate that the blockade of IL-6 signalling combined with conventional radiotherapy could augment the treatment response and survival rate in patients with radioresistant OSCC. Nature Publishing Group 2016-11-08 2016-10-13 /pmc/articles/PMC5104896/ /pubmed/27736845 http://dx.doi.org/10.1038/bjc.2016.327 Text en Copyright © 2016 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Translational Therapeutics
Matsuoka, Yuichiro
Nakayama, Hideki
Yoshida, Ryoji
Hirosue, Akiyuki
Nagata, Masashi
Tanaka, Takuya
Kawahara, Kenta
Sakata, Junki
Arita, Hidetaka
Nakashima, Hikaru
Shinriki, Satoru
Fukuma, Daiki
Ogi, Hidenao
Hiraki, Akimitsu
Shinohara, Masanori
Toya, Ryo
Murakami, Ryuji
IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma
title IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma
title_full IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma
title_fullStr IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma
title_full_unstemmed IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma
title_short IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma
title_sort il-6 controls resistance to radiation by suppressing oxidative stress via the nrf2-antioxidant pathway in oral squamous cell carcinoma
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104896/
https://www.ncbi.nlm.nih.gov/pubmed/27736845
http://dx.doi.org/10.1038/bjc.2016.327
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