Open AccessRole of autophagy in high linear energy transfer radiation‐induced cytotoxicity to tumor cells
Author(s) -
Jin Xiaodong,
Liu Yan,
Ye Fei,
Liu Xiongxiong,
Furusawa Yoshiya,
Wu Qingfeng,
Li Feifei,
Zheng Xiaogang,
Dai Zhongying,
Li Qiang
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12422
Subject(s) - autophagy , radiosensitivity , linear energy transfer , radiation therapy , apoptosis , programmed cell death , pi3k/akt/mtor pathway , cancer research , radiation sensitivity , cancer cell , microbiology and biotechnology , chemistry , irradiation , cytotoxicity , protein kinase b , cell , cell culture , cancer , biology , ion , medicine , biochemistry , in vitro , physics , genetics , organic chemistry , nuclear physics
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 PI 3 K / A kt 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.