Combination celecoxib and temozolomide in C6 rat glioma orthotopic model

The purpose of this study was to determine whether a combination treatment of temozolomide with celecoxib is effective in the rat orthotopic glioma model. After stereotactic injection of C6/LacZ rat glioma cells into the Sprague Dawley rat brain, the rats were randomly assigned to four treatment groups [group 1, control treatment; group 2, celecoxib (25 mg/kg p.o. everyday) alone; group 3, temozolomide (7.5 mg/kg i.p. for 5 days at 2nd week) alone; group 4, a combination of celecoxib and temozolomide]. Rats were sacrificed 18 days after treatment, and the body weight, tumor volume, tumor cell proliferation, microvessel densities, and apoptosis were evaluated. There was a significant reduction of tumor volume in combination group compared to control or single-agent therapy. The median tumor volume was estimated to be 111.5 mm ³(control), 65.0 mm³(celecoxib), 71.8 mm ³(temozolomide) and 18.7 mm³(combination). In the combination group, there was increased tumor cell apoptosis as well as decreased microvessel density and tumor cell proliferation relative to the control and single-agent therapy (P<0.05). Collectively, the data suggest that the combination celecoxib and temozolomide may provide a novel and effective approach to the treatment of glioblastoma.