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

J Neurosurg. 2005 Sep;103(3):508-17. doi: 10.3171/jns.2005.103.3.0508.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Blotting, Western
  • Celecoxib
  • Cell Proliferation
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Proteins
  • Meningeal Neoplasms / enzymology*
  • Meningeal Neoplasms / pathology
  • Meningioma / enzymology*
  • Meningioma / pathology
  • Middle Aged
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Pyrazoles / pharmacology*
  • Sulfonamides / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Membrane Proteins
  • Pyrazoles
  • Sulfonamides
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Celecoxib