Carbon ions induce autophagy effectively through stimulating the unfolded protein response and subsequent inhibiting Akt phosphorylation in tumor cells.
Heavy ion beams have advantages over conventional radiation in radiotherapy due to their superb biological effectiveness and dose conformity. However, little information is currently available concerning the cellular and molecular basis for heavy ion radiation-induced autophagy. In this study, human glioblastoma SHG44 and cervical cancer HeLa cells were irradiated with carbon ions of different linear energy transfers (LETs) and X-rays. Our results revealed increased LC3-II and decreased p62 levels in SHG44 and HeLa cells post-irradiation, indicating marked induction of autophagy. The autophagic level of tumor cells after irradiation increased in a LET-dependent manner and was inversely correlated with the sensitivity to radiations of various qualities. Furthermore, we demonstrated that high-LET carbon ions stimulated the unfolded protein response (UPR) and mediated autophagy via the UPR-eIF2α-CHOP-Akt signaling axis. High-LET carbon ions more severely inhibited Akt-mTOR through UPR to effectively induce autophagy. Thus, the present data could serve as an important radiobiological basis to further understand the molecular mechanisms by which high-LET radiation induces cell death.
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.
Xiaodong
X
Jin
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
Feifei
F
Li
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
Xiaogang
X
Zheng
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
Yan
Y
Liu
Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, Chiba 263-8555, Japan.
Ryoichi
R
Hirayama
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.
Xiongxiong
X
Liu
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.
Ping
P
Li
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.
Ting
T
Zhao
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.
Zhongying
Z
Dai
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.
Qiang
Q
Li
D001343:Autophagy / Q000187:drug effects*; D002244:Carbon; D015536:Down-Regulation / Q000528:radiation effects; D004789:Enzyme Activation / Q000528:radiation effects; D006367:HeLa Cells; D020450:Heavy Ions; D006801:Humans; D009374:Neoplasms, Experimental / Q000201:enzymology* / Q000473:pathology* / Q000532:radiotherapy; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D010766:Phosphorylation / Q000528:radiation effects; D056811:Unfolded Protein Response / Q000528:radiation effects*
D002244:Carbon; D051058:Oncogene Protein v-akt