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Published in: Journal of Neuro-Oncology 2/2016

01-04-2016 | Laboratory Investigation

Combination treatment with fasudil and clioquinol produces synergistic anti-tumor effects in U87 glioblastoma cells by activating apoptosis and autophagy

Authors: Mingliang He, Ming Luo, Qingyu Liu, Jingkao Chen, Kaishu Li, Meiguang Zheng, Yinlun Weng, Leping Ouyang, Anmin Liu

Published in: Journal of Neuro-Oncology | Issue 2/2016

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Abstract

Survival of patients with glioblastoma (GBM) remains poor, and novel treatment methods are urgently needed. In this study, we tested the effects of a combination of fasudil, a ROCK inhibitor, and clioquinol, an 8-hydroxyquinoline derivative with antimicrobial properties, on human GBM U87 cells. Combination treatment synergistically inhibited the viability of glioma cells but not mouse normal neuron HT22 cells and significantly induced mitochondria-mediated apoptosis. Moreover, the combination was also found to trigger macro-autophagy (henceforth referred to as autophagy) by increasing the expression levels of several proteins involved in the induction of autophagy. Further studies showed that 3-methyladenine (3-MA) or chloroquine (CQ), two autophagy inhibitors, abrogated the cytotoxic effects of the combination treatment as well as the autophagy. Overall, we demonstrated that fasudil and clioquinol show synergistic anti-cancer effects, providing evidence for the further development of combination therapy for GBM.
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Metadata
Title
Combination treatment with fasudil and clioquinol produces synergistic anti-tumor effects in U87 glioblastoma cells by activating apoptosis and autophagy
Authors
Mingliang He
Ming Luo
Qingyu Liu
Jingkao Chen
Kaishu Li
Meiguang Zheng
Yinlun Weng
Leping Ouyang
Anmin Liu
Publication date
01-04-2016
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 2/2016
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-015-2044-2

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