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Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells

By Irene Bijnsdorp, Jaap van den Berg, Gitta Kuipers, Laurine Wedekind, Ben Slotman, Johannes van Rijn, M. Lafleur and Peter Sminia

Abstract

The COX-2 protein is frequently overexpressed in human malignant gliomas. This expression has been associated with their aggressive\ud growth characteristics and poor prognosis for patients. Targeting the COX-2 pathway might improve glioma therapy. In this\ud study, the effects of the selective COX-2 inhibitor meloxicam alone and in combination with irradiation were investigated\ud on human glioma cells in vitro. A panel of three glioma cell lines (D384, U87 and U251) was used in the experiments from which U87 cells expressed constitutive\ud COX-2. The response to meloxicam and irradiation (dose-range of 0–6 Gy) was determined by the clonogenic assay, cell proliferation\ud was evaluated by growth analysis and cell cycle distribution by FACS. 24–72 h exposure to 250–750 μM meloxicam resulted in\ud a time and dose dependent growth inhibition with an almost complete inhibition after 24 h for all cell lines. Exposure to\ud 750 μM meloxicam for 24 h increased the fraction of cells in the radiosensitive G2/M cell cycle phase in D384 (18–27%) and U251 (17–41%) cells. 750 μM meloxicam resulted in radiosensitization of D384 (DMF:2.19)\ud and U87 (DMF:1.25) cells, but not U251 cells (DMF:1.08). The selective COX-2 inhibitor meloxicam exerted COX-2 independent\ud growth inhibition and radiosensitization of human glioma cells

Year: 2007
DOI identifier: 10.1007/s11060-007-9385-4
OAI identifier: oai:dare.ubvu.vu.nl:1871/11450
Provided by: DSpace at VU

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