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.

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 (P = 0.0495), 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.

• Authors: Michiyuki Hakozaki, Takahiro Tajino, Shinichi Konno, Shinichi Kikuchi, Hitoshi Yamada, Michiro Yanagisawa, Jun Nishida, Hiroyuki Nagasawa, Takashi Tsuchiya, Akira Ogose, Masafumi Abe, Hiroshi Hojo
• Journal: PloS one (PLoS One) Vol. 9 Issue 2 Pg. e88035 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24516579 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Caspase Inhibitors
• Cyclooxygenase 2 Inhibitors
• Etodolac
• Cyclooxygenase 2
• PTGS2 protein, human
• Caspases

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Apoptosis (drug effects)
• Caspase Inhibitors (pharmacology)
• Caspases (metabolism)
• Cell Line, Tumor
• Cell Shape (drug effects)
• Cyclooxygenase 2 (metabolism)
• Cyclooxygenase 2 Inhibitors (pharmacology)
• DNA Fragmentation (drug effects)
• Enzyme Activation (drug effects)
• Etodolac (pharmacology, therapeutic use)
• Female
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Multivariate Analysis
• Nerve Sheath Neoplasms (enzymology, pathology)
• Young Adult