Celecoxib inhibits meningioma tumor growth in a mouse xenograft model.
BACKGROUND
Treatments for recurrent meningiomas are limited. We previously demonstrated universal expression of COX-2 in meningiomas and dose-dependent growth inhibition in vitro with celecoxib, a COX-2 inhibitor. We therefore tested the effects of celecoxib on meningioma growth in a mouse xenograft model.


METHODS
Meningioma cell lines (IOMM-Lee, CH157-MN, WHO grade I primary cultured tumor) were transplanted into flanks of nude mice fed mouse chow with celecoxib at varying concentrations (0, 500, 1000, 1500 ppm) ad libitum. Tumors were measured biweekly and processed for MIB-1, Factor VIII, COX-2, and VEGF, and assayed with transferase-mediated dUTP-biotin nick-end labeling (TUNEL).


RESULTS
Celecoxib reduced growth of mean tumor volume by 66% (P < .05), 25% (P > .05), and 65% (P < .05) compared with untreated controls in IOMM-Lee, CH157-MN, and benign tumors, respectively. IOMM-Lee tumors removed from celecoxib treatment regained a growth rate similar to the control. Blood vessel density decreased and apoptotic cells increased in treated flank tumors. Diminished COX-2 expression and VEGF were observed in treated IOMM-Lee tumors. Mean plasma celecoxib levels were 845, 1540, and 2869 ng/mL, for low-, medium-, and high-dose celecoxib, respectively.


CONCLUSIONS
Celecoxib inhibits meningioma growth in vivo at plasma levels achievable in humans. Celecoxib-treated tumors were less vascular with increased apoptosis. IOMM-Lee tumors treated with celecoxib showed decreased COX-2 and VEGF expression. COX-2 inhibitors may have a role in the treatment of recurrent meningiomas.
Ragel
Brian T
BT
Department of Neurosurgery, University of Utah, Salt Lake City, Utah 84132, USA.
Jensen
Randy L
RL
Gillespie
David L
DL
Prescott
Stephen M
SM
Couldwell
William T
WT
D000818:Animals; D017209:Apoptosis; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D005169:Factor VIII / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D008577:Meningeal Neoplasms / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D008579:Meningioma / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008819:Mice, Nude; D011720:Pyrazoles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D016861:Cyclooxygenase Inhibitors; D019394:Ki-67 Antigen; D011720:Pyrazoles; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D005169:Factor VIII; D051546:Cyclooxygenase 2; D000068579:Celecoxib