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Expression of cyclooxygenase 2
(COX-2) in human glioma and in vitro inhibition by a specific COX-2 inhibitor,
NS-398
Joki T, Heese O, Nikas DC, Bello L, Zhang J, Kraeft SK,
Seyfried NT, Abe T, Chen LB, Carroll RS, Black PM
Brain Tumor Research Center, Brigham and Women's
Hospital, The Children's Hospital, Harvard Medical School, Boston, Massachusetts
02115, USA
The up-regulation of cyclooxygenase 2 (COX-2) expression is a
frequent occurrence in a variety of different tumors.
In this study, COX-2 protein expression was investigated in 50 glioma and 3
normal brain specimens by immunohistochemistry.
Expression of COX-2 protein was observed in all normal brain and glioma
specimens by immunohistochemistry, regardless of histological grade.
The immunoreactive score was significantly higher in high-grade glioma than
low-grade glioma and normal brain specimens.
For a subset of these tumors (nine gliomas and three normal brain), Western blot
analysis was also performed.
COX-2 protein was detected in all specimens by Western blot analysis.
The effect of the specific COX-2 inhibitor NS-398 on monolayer cell cultures and
three-dimensional glioma spheroids was investigated using U-87MG and U-251MG
human glioblastoma cell lines.
The proliferation rate was assessed in monolayer cultures.
In addition, a growth assay, a migration assay, an apoptosis assay, and a tumor
invasion assay were performed in a three-dimensional spheroid culture system.
NS-398 was able to reduce the proliferation of monolayer cell cultures, as well
as the growth of spheroids and tumor cell migration, in a dose-dependent manner.
There was also a moderate increase in the number of apoptotic cells in the
treated spheroids.
NS-398 did not have an inhibitory effect on tumor invasion in the coculture
spheroid system.
Our study provides evidence that COX-2 is up-regulated in the majority of
high-grade gliomas and that a potential role of COX-2 inhibitors as an adjuvant
therapy for brain tumors may exist.
PMID: 10987308 [PubMed - indexed for MEDLINE]
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