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Celecoxib inhibits meningioma tumor growth in a mouse xenograft model
Author(s) -
Ragel Brian T.,
Jensen Randy L.,
Gillespie David L.,
Prescott Stephen M.,
Couldwell William T.
Publication year - 2006
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.22441
Subject(s) - celecoxib , medicine , apoptosis , in vivo , angiogenesis , tunel assay , vascular endothelial growth factor , cancer , cancer research , pathology , endocrinology , immunohistochemistry , biology , vegf receptors , biochemistry , microbiology and biotechnology
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. Cancer 2007;109:588–597. © 2006 American Cancer Society.