Suppression of Autophagy Enhanced Growth Inhibition and Apoptosis of Interferon-β in Human Glioma Cells
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  • 作者:Yubin Li (1) (2)
    Haiyan Zhu (1)
    Xian Zeng (1)
    Jiajun Fan (1)
    Xiaolu Qian (3)
    Shaofei Wang (1)
    Ziyu Wang (1)
    Yun Sun (1)
    Xiaodan Wang (4)
    Weiwu Wang (2)
    Dianwen Ju (1) (5)
  • 关键词:Autophagy ; IFN ; β ; Glioma cells ; Growth inhibition ; Apoptosis
  • 刊名:Molecular Neurobiology
  • 出版年:2013
  • 出版时间:June 2013
  • 年:2013
  • 卷:47
  • 期:3
  • 页码:1000-1010
  • 全文大小:710KB
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  • 作者单位:Yubin Li (1) (2)
    Haiyan Zhu (1)
    Xian Zeng (1)
    Jiajun Fan (1)
    Xiaolu Qian (3)
    Shaofei Wang (1)
    Ziyu Wang (1)
    Yun Sun (1)
    Xiaodan Wang (4)
    Weiwu Wang (2)
    Dianwen Ju (1) (5)

    1. Department of Biosynthesis, School of Pharmacy, Fudan University, Shanghai, 201203, China
    2. Key Laboratory of Microbiological Engineering of Agricultural Environment, Ministry of Agriculture, Department of Microbiology, College of Life Science, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, China
    3. College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, China
    4. School of Life Science and Technology, Tongji University, Shanghai, 200092, China
    5. The Key Laboratory of Smart Drug Delivery, Ministry of Education & The People’s Liberation Army, School of Pharmacy, Fudan University, Shanghai, 201203, China
文摘
Interferon-beta (IFN-β) is a cytokine with anti-viral, anti-proliferative, and immunomodulatory effects. In this study, we investigated the effects of IFN-β on the induction of autophagy and the relationships among autophagy, growth inhibition, and apoptosis induced by IFN-β in human glioma cells. We found that IFN-β induced autophagosome formation and conversion of microtubule associated protein 1 light chain 3 (LC3) protein, whereas it inhibited cell growth through caspase-dependent cell apoptosis. The Akt/mTOR signaling pathway was involved in autophagy induced by IFN-β. A dose- and time-dependent increase of p-ERK 1/2 expression was also observed in human glioma cells treated with IFN-β. Autophagy induced by IFN-β was suppressed when p-ERK1/2 was impaired by treatment with U0126. We also demonstrated that suppression of autophagy significantly enhanced growth inhibition and cell apoptosis induced by IFN-β, whereas inhibition of caspase-dependent cell apoptosis impaired autophagy induced by IFN-β. Collectively, these findings indicated that autophagy induced by IFN-β was associated with the Akt/mTOR and ERK 1/2 signaling pathways, and inhibition of autophagy could enhance the growth inhibitory effects of IFN-β and increase apoptosis in human glioma cells. Together, these findings support the possibility that autophagy inhibitors may improve IFN-β therapy for gliomas.

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