Role of autophagy in high linear energy transfer radiation-induced cytotoxicity to tumor cells

Authors

  • Xiaodong Jin,

    1. Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
    2. Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou, China
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  • Yan Liu,

    1. Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
    2. Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou, China
    3. University of Chinese Academy of Sciences, Beijing, China
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  • Fei Ye,

    1. Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
    2. Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou, China
    3. University of Chinese Academy of Sciences, Beijing, China
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  • Xiongxiong Liu,

    1. Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
    2. Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou, China
    3. University of Chinese Academy of Sciences, Beijing, China
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  • Yoshiya Furusawa,

    1. Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan
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  • Qingfeng Wu,

    1. Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
    2. Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou, China
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  • Feifei Li,

    1. Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
    2. Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou, China
    3. University of Chinese Academy of Sciences, Beijing, China
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  • Xiaogang Zheng,

    1. Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
    2. Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou, China
    3. University of Chinese Academy of Sciences, Beijing, China
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  • Zhongying Dai,

    1. Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
    2. Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou, China
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  • Qiang Li

    Corresponding author
    1. Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
    2. Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou, China
    • Correspondence

      Qiang Li, Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road,

      Lanzhou 730000, Gansu Province, China.

      Tel: +86-931-4969316; Fax: +86-931-8272100;

      E-mail: liqiang@impcas.ac.cn

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  • Funding Information

    National Basic Research Program of China (973 Program) (2010CB834203). Key Project of National Natural Science Foundation of China (U1232207). National Natural Science Foundation of China (10905080, 11075191 and 11205217). Western Talents Program of the Chinese Academy of Sciences (O962030XBO). Gansu Provincial Funds for Distinguished Young Scientists (1111RJDA010).

Abstract

Heavy-ion radiotherapy has a potential advantage over conventional radiotherapy due to improved dose distribution and a higher biological effectiveness in cancer therapy. However, there is a little information currently available on the cellular and molecular basis for heavy-ion irradiation-induced cell death. Autophagy, as a novel important target to improve anticancer therapy, has recently attracted considerable attention. In this study, the effect of autophagy induced by high linear energy transfer (LET) carbon ions was examined in various tumor cell lines. To our knowledge, our study is the first to reveal that high-LET carbon ions could induce autophagy in various tumor cells effectively, and the autophagic level in the irradiated cells increased in a dose- and LET-dependent manner. The ability of carbon ions to inhibit the activation of the PI3K/Akt pathway rose with increasing their LET. Moreover, modulation of autophagy in tumor cells could modify their sensitivity to high-LET radiation, and inhibiting autophagy accelerated apoptotic cell death, resulting in an increase in radiosensitivity. Our data imply that targeting autophagy might enhance the effectiveness of heavy-ion radiotherapy.

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