Celecoxib inhibits meningioma tumor growth in a mouse xenograft model.
Cancer
; 109(3): 588-97, 2007 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-17177201
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Sulfonamidas
/
Inibidores de Ciclo-Oxigenase
/
Neoplasias Meníngeas
/
Meningioma
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Cancer
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos