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Impact of Hypoxia on Carbon Ion Therapy in Glioblastoma Cells: Modulation by LET and Hypoxia-Dependent Genes.
Valable, Samuel; Gérault, Aurélie N; Lambert, Gaëlle; Leblond, Marine M; Anfray, Clément; Toutain, Jérôme; Bordji, Karim; Petit, Edwige; Bernaudin, Myriam; Pérès, Elodie A.
Affiliation
  • Valable S; UNICAEN, CNRS, CEA, ISTCT/CERVOxy group, GIP Cyceron, Normandie Univ, 14000 Caen, France.
  • Gérault AN; UNICAEN, CNRS, CEA, ISTCT/CERVOxy group, GIP Cyceron, Normandie Univ, 14000 Caen, France.
  • Lambert G; UNICAEN, CNRS, CEA, ISTCT/CERVOxy group, GIP Cyceron, Normandie Univ, 14000 Caen, France.
  • Leblond MM; UNICAEN, CNRS, CEA, ISTCT/CERVOxy group, GIP Cyceron, Normandie Univ, 14000 Caen, France.
  • Anfray C; UNICAEN, CNRS, CEA, ISTCT/CERVOxy group, GIP Cyceron, Normandie Univ, 14000 Caen, France.
  • Toutain J; UNICAEN, CNRS, CEA, ISTCT/CERVOxy group, GIP Cyceron, Normandie Univ, 14000 Caen, France.
  • Bordji K; UNICAEN, CNRS, CEA, ISTCT/CERVOxy group, GIP Cyceron, Normandie Univ, 14000 Caen, France.
  • Petit E; UNICAEN, CNRS, CEA, ISTCT/CERVOxy group, GIP Cyceron, Normandie Univ, 14000 Caen, France.
  • Bernaudin M; UNICAEN, CNRS, CEA, ISTCT/CERVOxy group, GIP Cyceron, Normandie Univ, 14000 Caen, France.
  • Pérès EA; UNICAEN, CNRS, CEA, ISTCT/CERVOxy group, GIP Cyceron, Normandie Univ, 14000 Caen, France.
Cancers (Basel) ; 12(8)2020 Jul 23.
Article in En | MEDLINE | ID: mdl-32718037
Tumor hypoxia is known to limit the efficacy of ionizing radiations, a concept called oxygen enhancement ratio (OER). OER depends on physical factors such as pO2 and linear energy transfer (LET). Biological pathways, such as the hypoxia-inducible transcription factors (HIF), might also modulate the influence of LET on OER. Glioblastoma (GB) is resistant to low-LET radiation (X-rays), due in part to the hypoxic environment in this brain tumor. Here, we aim to evaluate in vitro whether high-LET particles, especially carbon ion radiotherapy (CIRT), can overcome the contribution of hypoxia to radioresistance, and whether HIF-dependent genes, such as erythropoietin (EPO), influence GB sensitivity to CIRT. Hypoxia-induced radioresistance was studied in two human GB cells (U251, GL15) exposed to X-rays or to carbon ion beams with various LET (28, 50, 100 keV/µm), and in genetically-modified GB cells with downregulated EPO signaling. Cell survival, radiobiological parameters, cell cycle, and ERK activation were assessed under those conditions. The results demonstrate that, although CIRT is more efficient than X-rays in GB cells, hypoxia can limit CIRT efficacy in a cell-type manner that may involve differences in ERK activation. Using high-LET carbon beams, or targeting hypoxia-dependent genes such as EPO might reduce the effects of hypoxia.
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Cancers (Basel) Year: 2020 Document type: Article Affiliation country: France Country of publication: Switzerland

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Cancers (Basel) Year: 2020 Document type: Article Affiliation country: France Country of publication: Switzerland