Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells.
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 0-6 Gy) was determined by the clonogenic assay, cell proliferation was evaluated by growth analysis and cell cycle distribution by FACS. 24-72 h exposure to 250-750 microM meloxicam resulted in a time and dose dependent growth inhibition with an almost complete inhibition after 24 h for all cell lines. Exposure to 750 microM meloxicam for 24 h increased the fraction of cells in the radiosensitive G(2)/M cell cycle phase in D384 (18-27%) and U251 (17-41%) cells. 750 microM 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.
Bijnsdorp
Irene V
IV
Department of Radiation Oncology, Division Radiobiology, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands.
van den Berg
Jaap
J
Kuipers
Gitta K
GK
Wedekind
Laurine E
LE
Slotman
Ben J
BJ
van Rijn
Johannes
J
Lafleur
M Vincent M
MV
Sminia
Peter
P
D015153:Blotting, Western; D001932:Brain Neoplasms / Q000201:enzymology / Q000532:radiotherapy*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005720:Gamma Rays; D005910:Glioma / Q000201:enzymology / Q000532:radiotherapy*; D006801:Humans; D000077239:Meloxicam; D011838:Radiation-Sensitizing Agents; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay
D052246:Cyclooxygenase 2 Inhibitors; D011838:Radiation-Sensitizing Agents; D013843:Thiazines; D013844:Thiazoles; D051546:Cyclooxygenase 2; D000077239:Meloxicam