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Ubiquitous expression of cyclooxygenase-2 in meningiomas and decrease in cell growth following in vitro treatment with the inhibitor celecoxib: potential therapeutic application.

Brian T Ragel·Randy L Jensen·David L Gillespie·Stephen M Prescott·William T Couldwell
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Abstract

OBJECT: 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.

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AdultAgedAged, 80 and overApoptosisBlotting, WesternCelecoxibCell ProliferationCyclooxygenase 2Cyclooxygenase 2 InhibitorsCyclooxygenase InhibitorsDose-Response Relationship, DrugFemaleHumansImmunohistochemistryMaleMembrane ProteinsMeningeal NeoplasmsMeningiomaMiddle AgedProstaglandin-Endoperoxide SynthasesPyrazolesSulfonamidesTumor Cells, CulturedJournal ArticleResearch Support, Non-U.S. Gov't

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Brian T Ragel, Randy L Jensen, David L Gillespie, Stephen M Prescott, William T Couldwell. 2005. Ubiquitous expression of cyclooxygenase-2 in meningiomas and decrease in cell growth following in vitro treatment with the inhibitor celecoxib: potential therapeutic application.. https://doi.org/10.3171/jns.2005.103.3.0508

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