%0 Journal Article
%T 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
%A Michiyuki Hakozaki
%A Takahiro Tajino
%A Shinichi Konno
%A Shinichi Kikuchi
%A Hitoshi Yamada
%A Michiro Yanagisawa
%A Jun Nishida
%A Hiroyuki Nagasawa
%A Takashi Tsuchiya
%A Akira Ogose
%A Masafumi Abe
%A Hiroshi Hojo
%J PLOS ONE
%D 2014
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0088035
%X 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 (¡Ý50% 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.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0088035