title: Reoxygenation Reverses Hypoxia-related Radioresistance in Head and Neck Cancer Cell Lines.
abstract: OBJECTIVE
  Head and neck cancer (HNC) is characterized by epidermal growth factor receptor (EGFR) overexpression and radiotherapy (RT) resistance. Cancer cells are able to survive and proliferate in hypoxic conditions. Hypoxia can be transiently interrupted by phases of reoxygenation. This work aimed to analyze the reoxygenation effect on proliferation in response to radiation in HNC cells.
  
  
  METHODS
  HNC cell lines CAL33 and CAL166 were subjected to an 8-Gy radiation dose in hypoxia and/or after reoxygenation. Cell proliferation and molecular factors involved in response to treatments were studied.
  
  
  RESULTS
  Cytotoxicity test confirmed radioresistance in hypoxia and highlighted that reoxygenation before RT restores sensitivity in both cell lines. Our results showed a similar proliferation inhibition effect and EGFR modulation but a different cell death mechanism in the two cell lines after treatment.
  
  
  CONCLUSIONS
  Reoxygenation before RT rescued radiosensitivity in HNC cells.
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Tonissi
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Lattanzio
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Astesana
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cavicchioli
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Ghiglia
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Martino
authors.initials: M
authors.lastname: Monteverde
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vivenza
authors.affiliation: Radiotherapy Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Gianello
authors.affiliation: Radiotherapy Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Elvio
authors.initials: E
authors.lastname: Russi
authors.affiliation: Medical Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Merlano
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy lonigro.c@ospedale.cuneo.it.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Lo Nigro
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004720:Endonucleases / Q000096:biosynthesis / Q000235:genetics; D066246:ErbB Receptors / Q000096:biosynthesis / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018773:Genes, erbB-1 / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010100:Oxygen / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C512478:EGFR protein, human; D066246:ErbB Receptors; C071447:ERCC1 protein, human; D004720:Endonucleases; D010100:Oxygen
keywords: Head neck cancer; hypoxia; radiotherapy; reoxygenation