title: ROS/Autophagy/Nrf2 Pathway Mediated Low-Dose Radiation Induced Radio-Resistance in Human Lung Adenocarcinoma A549 Cell.
abstract: Low-dose ionizing radiation (LDIR) can induce radio-resistance to following high dose radiation in various mammalian cells. The protective role of LDIR has been thought to be associated with the overall outcomes of cancer radiotherapy. NF-E2 related factor 2 (Nrf2) is a transcription factor that plays pivotal roles in maintaining cellular oxidative equilibrium. Since oxidative stress has been indicated to be a mediator of LDIR induced radio-resistance, the role of Nrf2 in this process was investigated in this research. Our results showed that in human lung adenocarcinoma A549 cell, 5cGy alpha particle induced radio-resistance to following 75cGy alpha particle radiation. The expression level of Nrf2 and its target Heme Oxygenase-1(HO-1) increased after 5cGy radiation. Both the shRNA of Nrf2 and the chemical inhibitor of HO-1 suppressed the induced radio-resistance, indicating the involvement of Nrf2 antioxidant pathway in this process. Further, we found 5cGy radiation stimulated autophagy process in A549. Inhibition of the autophagy process resulted in suppression of the radio-resistance and the induced expression of Nrf2 and HO-1. ROS scavenger N-acetyl-L-cysteine (NAC) blocked the autophagy process induced by 5cGy alpha particle, the upregulation of Nrf2 and HO-1, as well as the induced radio-resistance. In conclusion, ROS elevation caused by LDIR promoted Autophagy/Nrf2-HO-1 and conferred radio-resistance in A549.
authors.affiliation: 1. School of Nuclear Science and Technology, University of Science and Technology of China, Hefei 230027, PR China; ; 2. Key Laboratory of Ion Beam Bioengineering, Hefei Institute of Physical Science, Chinese Academy of Sciences and Anhui Province, No. 350 of Shushanhu Road, Hefei 230031, PR China.
authors.forename: Ni
authors.initials: N
authors.lastname: Chen
authors.affiliation: 1. School of Nuclear Science and Technology, University of Science and Technology of China, Hefei 230027, PR China; ; 2. Key Laboratory of Ion Beam Bioengineering, Hefei Institute of Physical Science, Chinese Academy of Sciences and Anhui Province, No. 350 of Shushanhu Road, Hefei 230031, PR China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Wu
authors.affiliation: 2. Key Laboratory of Ion Beam Bioengineering, Hefei Institute of Physical Science, Chinese Academy of Sciences and Anhui Province, No. 350 of Shushanhu Road, Hefei 230031, PR China.
authors.forename: Hang
authors.initials: H
authors.lastname: Yuan
authors.affiliation: 2. Key Laboratory of Ion Beam Bioengineering, Hefei Institute of Physical Science, Chinese Academy of Sciences and Anhui Province, No. 350 of Shushanhu Road, Hefei 230031, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000503:physiopathology* / Q000532:radiotherapy*; D000077192:Adenocarcinoma of Lung; D000704:Analysis of Variance; D015153:Blotting, Western; D002103:Cadaverine / Q000031:analogs & derivatives; D045744:Cell Line, Tumor; D003114:Colony-Forming Units Assay; D017931:DNA Primers / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000503:physiopathology* / Q000532:radiotherapy*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D011836:Radiation Tolerance / Q000187:drug effects* / Q000528:radiation effects*; D011839:Radiation, Ionizing; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D051547:Heme Oxygenase-1; C008542:monodansylcadaverine; D002103:Cadaverine
keywords: Autophagy; Low dose ionizing radiation; Nrf2; ROS; radio-resistance