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

Xin Zhang; Xiuting Liu; Wei Zhou; Mengdi Yang; Yang Ding; Qing Wang; Rong Hu

doi:10.1038/s41419-017-0251-9

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

Xin Zhang, Xiuting Liu, Wei Zhou, Mengdi Yang, Yang Ding, Qing Wang, Rong Hu

Section of Medical Oncology

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

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.

Original language	English
Article number	190
Journal	Cell Death and Disease
Volume	9
Issue number	2
DOIs	https://doi.org/10.1038/s41419-017-0251-9
State	Published - Feb 1 2018

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title = "Fasudil increases temozolomide sensitivity and suppresses temozolomide-resistant glioma growth via inhibiting ROCK2/ABCG2",

abstract = "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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T1 - Fasudil increases temozolomide sensitivity and suppresses temozolomide-resistant glioma growth via inhibiting ROCK2/ABCG2

AU - Zhang, Xin

AU - Liu, Xiuting

AU - Zhou, Wei

AU - Yang, Mengdi

AU - Ding, Yang

AU - Wang, Qing

AU - Hu, Rong

PY - 2018/2/1

Y1 - 2018/2/1

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

Abstract

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