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Celecoxib inhibits meningioma tumor growth in a mouse xenograft model
Brian T Ragel1, Randy L Jensen, David L Gillespie
1Department of Neurosurgery, University of Utah, Salt Lake City, Utah 84132, USA.
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.
Insights
Celecoxib, a COX-2 inhibitor, effectively reduced recurrent meningioma growth in a mouse model. This suggests potential for using COX-2 inhibitors in treating these challenging brain tumors.
Area of Science:
- Oncology
- Pharmacology
- Neurosurgery
Background:
- Recurrent meningiomas present limited treatment options.
- Cyclooxygenase-2 (COX-2) is universally expressed in meningiomas.
- In vitro studies showed celecoxib inhibits meningioma cell growth.
Purpose of the Study:
- To evaluate the efficacy of celecoxib in inhibiting meningioma growth in vivo.
- To assess the impact of celecoxib on tumor vascularity and apoptosis.
Main Methods:
- Meningioma cell lines were xenografted into nude mice.
- Mice received varying concentrations of celecoxib in their chow.
- Tumor growth, MIB-1, Factor VIII, COX-2, VEGF, and apoptosis (TUNEL) were analyzed.
Main Results:
- Celecoxib significantly reduced mean tumor volume in IOMM-Lee and benign tumors.
- Tumor growth resumed after celecoxib treatment cessation.
- Reduced tumor vascularity and increased apoptosis were observed in treated tumors.
- Diminished COX-2 and VEGF expression were noted in celecoxib-treated IOMM-Lee tumors.
Conclusions:
- Celecoxib demonstrates in vivo efficacy against meningioma growth at human-achievable plasma levels.
- Celecoxib treatment leads to decreased tumor vascularity and increased apoptosis.
- COX-2 inhibitors represent a potential therapeutic strategy for recurrent meningiomas.
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