Inhibitory Effect of IFN-β, on the Antitumor Activity of Celecoxib in U87 Glioma Model

Abstract

Interferon-beta, (IFN-beta) has been used in the treatment of cancers. Inhibition of the enzyme cyclooxygenase (COX) with celecoxib had a significantly suppressive effect on tumor growth, angiogenesis, and metastasis in a variety of tumors. The aim of this study was to elucidate the antiglioma effect of combined treatment with IFN-beta and celecoxib in U87 glioma model. The in vitro effects of IFN-beta (50-1,000 IU/mL) and celecoxib (50-250 microM) alone or combination of both on the proliferation and apoptosis of U87 cells were tested using MTT assay, FACS analysis and DNA condensation. To determine the in vivo effect, nude mice bearing intracerebral U87 xenograft inoculation were treated with IFN-beta intraperitoneally (2x10(5) IU/day for 15 days), celecoxib orally (5, 10 mg/kg) or their combination. IFN-beta or celecoxib showed an inhibitory effect on the proliferation of U87 cells. When U87 cells were treated with IFN-beta and celecoxib combination, it seemed that IFN-beta interrupted the antiproliferative and apoptotic activity of celecoxib. No additive effect was observed on the survival of the tumor bearing mice by the combination of IFN-beta and celecoxib. These results suggest that IFN-beta seems to inhibit the antiglioma effect of celecoxib, therefore combination of IFN-beta and celecoxib may be undesirable in the treatment of glioma.