Reoxygenation Reverses Hypoxia-related Radioresistance in Head and Neck Cancer Cell Lines

Anticancer Res. 2016 May;36(5):2211-5.

Abstract

Background/aim: 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.

Materials and 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.

Conclusion: Reoxygenation before RT rescued radiosensitivity in HNC cells.

Keywords: Head neck cancer; hypoxia; radiotherapy; reoxygenation.

MeSH terms

  • Apoptosis / drug effects
  • Carcinoma, Squamous Cell / pathology*
  • Cell Division / drug effects
  • Cell Hypoxia / drug effects*
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • Endonucleases / biosynthesis
  • Endonucleases / genetics
  • ErbB Receptors / biosynthesis
  • ErbB Receptors / physiology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genes, erbB-1 / drug effects
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Oxygen / pharmacology*
  • Radiation Tolerance / drug effects*

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Neoplasm Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • EGFR protein, human
  • ErbB Receptors
  • ERCC1 protein, human
  • Endonucleases
  • Oxygen