Sodium glycididazole enhances the radiosensitivity of laryngeal cancer cells through downregulation of ATM signaling pathway

Tumour Biol. 2016 May;37(5):5869-78. doi: 10.1007/s13277-015-4278-1. Epub 2015 Nov 9.

Abstract

The purpose of this study was to evaluate the radiation-enhancing effect of sodium glycididazole, and the corresponding mechanisms of action on laryngeal cancer cells. Two laryngeal cancer cell lines (Hep-2 and UT-SCC-19A) were irradiated with X-rays in the presence or absence of sodium glycididazole. Cell survival, DNA damage and repair, cell apoptosis, cell cycle distribution, expression of proteins related to cell cycle checkpoint, and apoptosis were measured. Significantly increased DNA damages, decreased cells in the G1 phase, arrested cells at G2/M phase, decreased DNA repair protein XRCC1 foci formation, and enhanced cell apoptosis were observed in laryngeal cell lines treated by sodium glycididazole combined with irradiation compared with the irradiation alone. The combined treatment downregulated the protein expressions of ataxia-telangiectasia mutated (ATM), p-ATM, CHK2, and P53 but upregulated the protein expressions of MDM2 and Cdk2. This study indicates that sodium glycididazole enhances the radiosensitivity of laryngeal cancer cells through downregulation of ATM signaling pathway in vitro and in vivo.

Keywords: ATM signaling pathway; Laryngeal cancer; Radiation-enhancing effect; Sodium glycididazole.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Ataxia Telangiectasia Mutated Proteins / metabolism*
  • Biomarkers, Tumor / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • DNA Repair / drug effects
  • Disease Models, Animal
  • Hep G2 Cells
  • Humans
  • Hypoxia / drug therapy
  • Hypoxia / metabolism
  • Imidazoles / pharmacology*
  • Laryngeal Neoplasms / metabolism*
  • Laryngeal Neoplasms / pathology
  • Mice
  • Radiation-Sensitizing Agents / pharmacology*
  • Signal Transduction / drug effects*
  • Tumor Burden / drug effects
  • Tumor Burden / radiation effects
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • Imidazoles
  • Radiation-Sensitizing Agents
  • sodium glycididazole
  • Ataxia Telangiectasia Mutated Proteins