Telomerase-specific oncolytic adenovirus: antitumor effects on radiation-resistant head and neck squamous cell carcinoma cells

Head Neck. 2014 Mar;36(3):411-8. doi: 10.1002/hed.23309. Epub 2013 Jun 1.

Abstract

Background: Radioresistance remains a critical issue in the use of radiotherapy for the treatment of head and neck squamous cell carcinoma (HNSCC). This study evaluated the efficacy of combination treatment with OBP-301, a telomerase-specific replication-selective adenovirus, and radiotherapy in overcoming radioresistance by examining its effect on radiation-resistant HNSCC cells.

Methods: Radiation-resistant HNSCC cells were treated with OBP-301 and radiation in vitro and in an orthotopic nude mouse model in vivo and synergism was assessed. Apoptosis and expression of MRN complex, which plays a key role in DNA repair machinery, were also analyzed.

Results: Infection with OBP-301 was found to enhance the antitumor efficacy of radiation both in vitro and in vivo by inhibiting MRN complex expression and increasing apoptosis induction.

Conclusion: Combined OBP-301 and radiation therapy seems to overcome radioresistance in HNSCC cells by inhibiting DNA repair machinery, and may thus be a novel therapeutic strategy for treating HNSCC.

Keywords: OBP-301; head and neck squamous cell carcinoma; radiation sensitivity; telomerase; virotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / metabolism*
  • Animals
  • Blotting, Western
  • Carcinoma, Squamous Cell / radiotherapy
  • Carcinoma, Squamous Cell / therapy*
  • DNA Repair / physiology
  • DNA Repair / radiation effects
  • Disease Models, Animal
  • Female
  • Head and Neck Neoplasms / radiotherapy
  • Head and Neck Neoplasms / therapy*
  • Humans
  • In Vitro Techniques
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplastic Cells, Circulating
  • Oncolytic Virotherapy / methods*
  • Radiation, Ionizing
  • Radiotherapy Dosage
  • Squamous Cell Carcinoma of Head and Neck
  • Telomerase / genetics
  • Telomerase / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Telomerase