Celecoxib Radiosensitizes the Human Cervical Cancer HeLa Cell Line via a Mechanism Dependent on Reduced cyclo-oxygenase-2 and Vascular Endothelial Growth Factor C Expression

OBJECTIVE: The effects of celecoxib, a selective cyclo-oxygenase-2 (COX-2) inhibitor, on He La cervical cancer cell growth and radiosensitivity were investigated. METHODS: Cytotoxicity was quantified using a 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium assay and effects on radiosensitivity were assessed using the lethal dose, quasi-threshold dose, fraction surviving after 2 Gy irradiation and the radiosensitization ratio (SER, based on average lethal dose) determined using a single-hit multitarget model. RESULTS: Celecoxib inhibited He La cell proliferation in a concentration- and time-dependent manner, with a half-maximal inhibitory concentration at 72 h of 44 mu mol/l. Treatment with 20 mu mol/l celecoxib for 72 h before irradiation was associated with an SER of 2.01. The SER of irradiated cells was 2.41 when treated with 40 mu mol/l celecoxib before irradiation, 1.89 when treated simultaneously and 1.44 when treated after irradiation. Celecoxib down-regulated COX-2 and vascular endothelial growth factor C (VEGF-C) expression evaluated immunohistochemically. CONCLUSION: Celecoxib pretreatment radiosensitizes He La cells via a mechanism dependent on down-regulation of COX-2 and VEGF-C.