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

Abstract

Objective: The effects of celecoxib, a selective cyclo-oxygenase-2 (COX-2) inhibitor, on HeLa 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, quasithreshold 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 HeLa cell proliferation in a concentration- and time-dependent manner, with a half-maximal inhibitory concentration at 72 h of 44 μmol/l. Treatment with 20 μmol/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 μmol/l celecoxib before irradiation, 1.89 when treated simultaneously and 1.44 when treated after irradiation. Celecoxib downregulated COX-2 and vascular endothelial growth factor C (VEGF-C) expression evaluated immunohistochemically.

Conclusion: Celecoxib pretreatment radiosensitizes HeLa cells via a mechanism dependent on down-regulation of COX-2 and VEGF-C.