Role of autophagy in high linear energy transfer radiation-induced cytotoxicity to tumor cells
Version of Record online: 23 MAY 2014
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Volume 105, Issue 7, pages 770–778, July 2014
How to Cite
Cancer Sci (2014) 770–778
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).
- Issue online: 14 JUL 2014
- Version of Record online: 23 MAY 2014
- Accepted manuscript online: 15 APR 2014 04:54AM EST
- Manuscript Accepted: 10 APR 2014
- Manuscript Revised: 9 APR 2014
- Manuscript Received: 27 JAN 2014
- National Basic Research Program of China. Grant Number: 2010CB834203
- Key Project of National Natural Science Foundation of China. Grant Number: U1232207
- National Natural Science Foundation of China. Grant Numbers: 10905080, 11075191, 11205217
- Western Talents Program of the Chinese Academy of Sciences. Grant Number: O962030XBO
- Distinguished Young Scientists. Grant Number: 1111RJDA010
- high-LET radiation;
- PI3K/Akt pathway;
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.