Fasudil increases temozolomide sensitivity and suppresses temozolomide-resistant glioma growth via inhibiting ROCK2/ABCG2

Resistance to temozolomide (TMZ) is a major clinical challenge in glioma treatment, but the mechanisms of TMZ resistance are poorly understood. Here, we provided evidence that ROCK2 acted redundantly to maintain resistance of TMZ in TMZ-resistant gliomas, and as a ROCK2 phosphorylation inhibitor, fa...

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Autores principales: Zhang, Xin, Liu, Xiuting, Zhou, Wei, Yang, Mengdi, Ding, Yang, Wang, Qing, Hu, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833824/
https://www.ncbi.nlm.nih.gov/pubmed/29416017
http://dx.doi.org/10.1038/s41419-017-0251-9
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author Zhang, Xin
Liu, Xiuting
Zhou, Wei
Yang, Mengdi
Ding, Yang
Wang, Qing
Hu, Rong
author_facet Zhang, Xin
Liu, Xiuting
Zhou, Wei
Yang, Mengdi
Ding, Yang
Wang, Qing
Hu, Rong
author_sort Zhang, Xin
collection PubMed
description Resistance to temozolomide (TMZ) is a major clinical challenge in glioma treatment, but the mechanisms of TMZ resistance are poorly understood. Here, we provided evidence that ROCK2 acted redundantly to maintain resistance of TMZ in TMZ-resistant gliomas, and as a ROCK2 phosphorylation inhibitor, fasudil significantly suppressed proliferation of TMZ-resistant gliomas in vivo and vitro via enhancing the chemosensitivity of TMZ. Additionally, the membrane translocation of ABCG2 was decreased with fasudil by ROCK2/moesin pathway. We also showed that fasudil suppressed the expression of ABCG2 via ROCK2/moesin/β-catenin pathway. Our results reveal an indispensable role for ROCK2 and provide strong evidence for the therapeutic use of fasudil in the clinical setting for TMZ-resistant gliomas.
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spelling pubmed-58338242018-03-06 Fasudil increases temozolomide sensitivity and suppresses temozolomide-resistant glioma growth via inhibiting ROCK2/ABCG2 Zhang, Xin Liu, Xiuting Zhou, Wei Yang, Mengdi Ding, Yang Wang, Qing Hu, Rong Cell Death Dis Article Resistance to temozolomide (TMZ) is a major clinical challenge in glioma treatment, but the mechanisms of TMZ resistance are poorly understood. Here, we provided evidence that ROCK2 acted redundantly to maintain resistance of TMZ in TMZ-resistant gliomas, and as a ROCK2 phosphorylation inhibitor, fasudil significantly suppressed proliferation of TMZ-resistant gliomas in vivo and vitro via enhancing the chemosensitivity of TMZ. Additionally, the membrane translocation of ABCG2 was decreased with fasudil by ROCK2/moesin pathway. We also showed that fasudil suppressed the expression of ABCG2 via ROCK2/moesin/β-catenin pathway. Our results reveal an indispensable role for ROCK2 and provide strong evidence for the therapeutic use of fasudil in the clinical setting for TMZ-resistant gliomas. Nature Publishing Group UK 2018-02-07 /pmc/articles/PMC5833824/ /pubmed/29416017 http://dx.doi.org/10.1038/s41419-017-0251-9 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhang, Xin
Liu, Xiuting
Zhou, Wei
Yang, Mengdi
Ding, Yang
Wang, Qing
Hu, Rong
Fasudil increases temozolomide sensitivity and suppresses temozolomide-resistant glioma growth via inhibiting ROCK2/ABCG2
title Fasudil increases temozolomide sensitivity and suppresses temozolomide-resistant glioma growth via inhibiting ROCK2/ABCG2
title_full Fasudil increases temozolomide sensitivity and suppresses temozolomide-resistant glioma growth via inhibiting ROCK2/ABCG2
title_fullStr Fasudil increases temozolomide sensitivity and suppresses temozolomide-resistant glioma growth via inhibiting ROCK2/ABCG2
title_full_unstemmed Fasudil increases temozolomide sensitivity and suppresses temozolomide-resistant glioma growth via inhibiting ROCK2/ABCG2
title_short Fasudil increases temozolomide sensitivity and suppresses temozolomide-resistant glioma growth via inhibiting ROCK2/ABCG2
title_sort fasudil increases temozolomide sensitivity and suppresses temozolomide-resistant glioma growth via inhibiting rock2/abcg2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833824/
https://www.ncbi.nlm.nih.gov/pubmed/29416017
http://dx.doi.org/10.1038/s41419-017-0251-9
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