Carbon ions induce autophagy effectively through stimulating the unfolded protein response and subsequent inhibiting Akt phosphorylation in tumor cells
Hirayama, Ryoichi1; Li, Qiang2,3; Jin, Xiaodong2,3; Li, Feifei2,3,4; Zheng, Xiaogang2,3,4; Liu, Yan2,3,4; Dai, Zhongying2,3; Zhao, Ting2,3; Li, Ping2,3; Liu, Xiongxiong2,3
刊名SCIENTIFIC REPORTS
2015-09-04
卷号5页码:10
ISSN号2045-2322
DOI10.1038/srep13815
英文摘要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-eIF2 alpha-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.
资助项目National Natural Science Foundation of China[11075191] ; National Natural Science Foundation of China[11205217] ; National Natural Science Foundation of China[U1232207]
WOS关键词ENDOPLASMIC-RETICULUM STRESS ; HEPATOMA HEPG2 CELLS ; HIGH-LET RADIATION ; CANCER-CELLS ; IONIZING-RADIATION ; THERAPY ; APOPTOSIS ; IRRADIATION ; MACHINERY ; SURVIVIN
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000360641000001
资助机构National Natural Science Foundation of China
内容类型期刊论文
源URL[http://ir.impcas.ac.cn/handle/113462/18572]  
专题近代物理研究所_医学物理研究室
近代物理研究所_生物物理研究室
通讯作者Li, Qiang
作者单位1.Natl Inst Radiol Sci, Res Ctr Charged Particle Therapy, Inage Ku, Chiba 2638555, Japan
2.Chinese Acad Sci, Inst Modern Phys, Lanzhou 730000, Peoples R China
3.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou 730000, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
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Hirayama, Ryoichi,Li, Qiang,Jin, Xiaodong,et al. Carbon ions induce autophagy effectively through stimulating the unfolded protein response and subsequent inhibiting Akt phosphorylation in tumor cells[J]. SCIENTIFIC REPORTS,2015,5:10.
APA Hirayama, Ryoichi.,Li, Qiang.,Jin, Xiaodong.,Li, Feifei.,Zheng, Xiaogang.,...&Liu, Xiongxiong.(2015).Carbon ions induce autophagy effectively through stimulating the unfolded protein response and subsequent inhibiting Akt phosphorylation in tumor cells.SCIENTIFIC REPORTS,5,10.
MLA Hirayama, Ryoichi,et al."Carbon ions induce autophagy effectively through stimulating the unfolded protein response and subsequent inhibiting Akt phosphorylation in tumor cells".SCIENTIFIC REPORTS 5(2015):10.
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