Ubiquitous expression of cyclooxygenase-2 in meningiomas and decrease in cell growth following in vitro treatment with the inhibitor celecoxib: potential therapeutic application.
OBJECTIVE
Meningiomas are the second most common symptomatic primary central nervous system tumor in adults. Findings of epidemiological studies link meningiomas with a history of head trauma, indicating a causal relationship between the inflammatory response and meningioma tumorigenesis. Cyclooxygenase-2 (COX-2), an inducible inflammatory enzyme, converts arachidonic acid to prostaglandins, which have angiogenic, cell-proliferative, and antiapoptotic effects. The authors investigated COX-2 expression in meningiomas and the effects of celecoxib, a COX-2 inhibitor, on meningioma cell growth in vitro.


METHODS
Four meningioma surgical specimens were immunohistochemically stained and graded (0 to 4) for COX-2. In addition, a Western blot analysis was performed to detect the presence of COX-2. Human meningioma cells grown in cell culture were treated with vehicle or celecoxib (0.25-1 mM). An immunohistochemical analysis of COX-2, a methylthiotetrazole cell proliferation assay, a TUNEL apoptosis assay, and a Western blot analysis for the proapoptotic protein BAX were performed in vitro. One hundred eleven (87%) of 128 benign meningiomas and six (86%) of seven atypical meningiomas displayed a high COX-2 immunoreactivity (Grade 4 staining). In the Western blot analysis all four surgical specimens (100%) stained positive for a 70-kD band consistent with COX-2. Celecoxib inhibited cell growth in a dose-dependent fashion and induced apoptosis by Day 2, with no change noted in the expression of the BAX protein.


CONCLUSIONS
The COX-2 enzyme is universally expressed in meningiomas. Celecoxib inhibits meningioma growth in vitro in a dose-dependent fashion, with evidence of apoptosis. Inhibitors of COX-2 may have a role in the treatment of recurrent meningiomas.
Ragel
Brian T
BT
Department of Neurosurgery, University of Utah; and Huntsman Cancer Institute, Salt Lake City, Utah 84132, USA.
Jensen
Randy L
RL
Gillespie
David L
DL
Prescott
Stephen M
SM
Couldwell
William T
WT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015153:Blotting, Western; D000068579:Celecoxib; D049109:Cell Proliferation; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins; D008577:Meningeal Neoplasms / Q000201:enzymology* / Q000473:pathology; D008579:Meningioma / Q000201:enzymology* / Q000473:pathology; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib