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Suppression of Autophagy Enhanced Growth Inhibition and Apoptosis of Interferon-β in Human Glioma Cells

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Abstract

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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Acknowledgments

This work was supported by Shanghai Science and Technology Funds (11431920104, 09XD1421800), National Science and Technology Major Project for Drug Discovery of Ministry of Science and Technology of China (2011ZX09102-001-27), and the National Key Basic Research Program of China (2013CB932502).

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Authors and Affiliations

  1. Department of Biosynthesis, School of Pharmacy, Fudan University, Shanghai, 201203, China

    Yubin Li, Haiyan Zhu, Xian Zeng, Jiajun Fan, Shaofei Wang, Ziyu Wang, Yun Sun & Dianwen Ju

  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

    Yubin Li & Weiwu Wang

  3. College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, China

    Xiaolu Qian

  4. School of Life Science and Technology, Tongji University, Shanghai, 200092, China

    Xiaodan Wang

  5. The Key Laboratory of Smart Drug Delivery, Ministry of Education & The People’s Liberation Army, School of Pharmacy, Fudan University, Shanghai, 201203, China

    Dianwen Ju

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  1. Yubin Li
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Correspondence to Dianwen Ju.

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Y.L. and H.Z. contributed equally to this work.

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Li, Y., Zhu, H., Zeng, X. et al. Suppression of Autophagy Enhanced Growth Inhibition and Apoptosis of Interferon-β in Human Glioma Cells. Mol Neurobiol 47, 1000–1010 (2013). https://doi.org/10.1007/s12035-013-8403-0

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