Combination treatment with fasudil and clioquinol produces synergistic anti-tumor effects in U87 glioblastoma cells by activating apoptosis and autophagy
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  • 作者:Mingliang He ; Ming Luo ; Qingyu Liu ; Jingkao Chen ; Kaishu Li
  • 关键词:Fasudil ; Clioquinol ; Synergistic effect ; Apoptosis ; Autophagy ; Glioblastoma
  • 刊名:Journal of Neuro-Oncology
  • 出版年:2016
  • 出版时间:April 2016
  • 年:2016
  • 卷:127
  • 期:2
  • 页码:261-270
  • 全文大小:3,123 KB
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  • 作者单位:Mingliang He (1)
    Ming Luo (2)
    Qingyu Liu (3)
    Jingkao Chen (4)
    Kaishu Li (1)
    Meiguang Zheng (1)
    Yinlun Weng (1)
    Leping Ouyang (1)
    Anmin Liu (1)

    1. Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China
    2. Department of Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China
    3. Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China
    4. School of Pharmaceutical Sciecnes, Sun Yat-Sen University, Guangzhou, 510006, China
  • 刊物类别:Medicine
  • 刊物主题:Medicine & Public Health
    Oncology
  • 出版者:Springer Netherlands
  • ISSN:1573-7373
文摘
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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