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

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

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Abstract

The COX-2 protein is frequently overexpressed in human malignant gliomas. This expression has been associated with their aggressive growth characteristics and poor prognosis for patients. Targeting the COX-2 pathway might improve glioma therapy. In this study, the effects of the selective COX-2 inhibitor meloxicam alone and in combination with irradiation were investigated 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 COX-2. The response to meloxicam and irradiation (dose-range of 0–6andnbsp;Gy) was determined by the clonogenic assay, cell proliferation was evaluated by growth analysis and cell cycle distribution by FACS. 24–72andnbsp;h exposure to 250–750 μM meloxicam resulted in a time and dose dependent growth inhibition with an almost complete inhibition after 24andnbsp;h for all cell lines. Exposure to 750andnbsp;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) and U87 (DMF:1.25) cells, but not U251 cells (DMF:1.08). The selective COX-2 inhibitor meloxicam exerted COX-2 independent growth inhibition and radiosensitization of human glioma cells.
Original languageEnglish
Pages (from-to)25-31
JournalJournal of Neuro-Oncology
Volume85
Issue number1
Publication statusPublished - 2007

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Bijnsdorp, I., Kuipers, G., Lafleur, M., Slotman, B., Sminia, P., van de Berg, J., ... Wedekind, L. (2007). Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells. Journal of Neuro-Oncology, 85(1), 25-31.