Overexpression of cyclooxygenase-2 in malignant peripheral nerve sheath tumor and selective cyclooxygenase-2 inhibitor-induced apoptosis by activating caspases in human malignant peripheral nerve sheath tumor cells.
PLoS One
; 9(2): e88035, 2014.
Article
in En
| MEDLINE
| ID: mdl-24516579
ABSTRACT
BACKGROUND:
Cyclooxygenase-2 (COX-2) is a key enzyme in the conversion of arachidonic acid to prostanoids, and its activation is associated with carcinogenesis as well as inflammation. The antitumor effect of selective COX-2 inhibitors has been noted in various malignancies. Malignant peripheral nerve sheath tumor (MPNST) is a rare and aggressive soft tissue sarcoma for which effective treatments have not yet been established. The purpose of this study was to investigate a potential therapeutic role of COX-2 in MPNST.METHODS:
We evaluated the expression of COX-2 in 44 cases of high-grade MPNST using immunohistochemical staining and compared the staining results with the characteristics and outcome of the patients. We also investigated the antitumor effect of etodolac, a selective COX-2 inhibitor, on MPNST cells in vitro using the MPNST cell line, FMS-1.RESULTS:
Overexpression of COX-2 (≥50% positive cells) was observed in 29 cases (65.9%), was significantly associated with a poor overall survival (Pâ=â0.0495), and was considered an independent risk factor for a poor outcome by the results of both univariate and multivariate analysis. Etodolac induced apoptosis of FMS-1 cells through the activation of caspase-8, -9, and -3. Moreover, several caspase inhibitors significantly inhibited etodolac-induced apoptosis.CONCLUSIONS:
Selective COX-2 inhibitors including etodolac had an antitumor effect on MPNST cells, and their use holds promise as a novel therapeutic strategy for patients with MPNST to improve their prognoses.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Apoptosis
/
Nerve Sheath Neoplasms
/
Caspases
/
Cyclooxygenase 2
/
Cyclooxygenase 2 Inhibitors
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
PLoS One
Journal subject:
CIENCIA
/
MEDICINA
Year:
2014
Document type:
Article
Affiliation country: