Combined action of celecoxib and ionizing radiation in prostate cancer cells is independent of pro-apoptotic Bax

Background and purpose: The cyclooxygenase-2-inhibitor celecoxib has been shown to inhibit cell growth and to reduce prostatic intraepithelial neoplasia in mice. The drug Was suggested to increase efficacy of ionizing radiation. However, extent and mechanisms of the Suggested benefit of celecoxib on the radiation response are still unclear. The aim of the present study was to analyze cytotoxic efficacy of celecoxib in combination with irradiation on human prostate cancer cell lines and to define the importance of proapoptotic Bax in this process. Materials and methods: Induction of apoptosis and global and clonogenic cell survival upon irradation-(2-10Gy), celecoxib-(11-75 mu M) or combined treatment were evaluated in prostate cancer cells by fluorescence microscopy, WST-1 assay and standard colony formation assays. Results: Celecoxib <25 mu M caused morphological changes and growth inhibition without substantial apoptosis or radiosensitization in terms of decreased clonogenic cell survival. In contrast, celecoxib >= 25 mu M increased radiation-induced cell death and clonogenic kill. While radiation-induced clonogenic death was increased in the presence of Bax, effects of celecoxib or combined treatment were Bax independent. Conclusions: Our findings reveal Bax-independent beneficial effects of celecoxib on radiation-induced apoptosis and eradication of clonogenic prostate cancer cells in vitro providing a rationale for clinical evaluation of high-dose celecoxib in combination with irradiation in prostate cancer patients. (C) 2008 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 90 (2009) 413-421