Cooperative enhancement of radiosensitivity after combined treatment of 17-(allylamino)-17-demethoxygeldanamycin and celecoxib in human lung and colon cancer cell lines

Young Mee Kim, Hongryull Pyo

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

We investigated whether the combined treatment of 17-(allylamino)-17- demethoxygeldanamycin (17-AAG), an inhibitor of heat-shock protein 90 (hsp90), and celecoxib, an inhibitor of cyclooxygenase-2, can cooperatively enhance the radiosensitivity of various human cancer cells. Combined treatment with 17-AAG and celecoxib, at clinically relevant concentrations, cooperatively induced radiosensitization in all tested cancer cells, but not in normal cells. Cooperative radiosensitization by the drug combination was also shown in a human tumor xenograft system. We found that ataxia-telangiectasia and rad3-related (ATR) and ataxia-telangiectasia mutated (ATM) are novel client proteins of hsp90. Combined treatment with 17-AAG and celecoxib cooperatively induced downregulation of ATR and ATM. In conclusion, combined treatment with 17-AAG and celecoxib at clinically relevant concentrations may significantly enhance the therapeutic efficacy of ionizing radiation.

Original languageEnglish (US)
Pages (from-to)15-29
Number of pages15
JournalDNA and cell biology
Volume31
Issue number1
DOIs
StatePublished - Jan 1 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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