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

BackgroundCyclooxygenase-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.MethodsWe 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.ResultsOverexpression 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.ConclusionsSelective 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.

Growth Factors and COX2 Expression in Canine Perivascular Wall Tumors

“…This result was expected since COX2 expression has been reported mainly in epithelial tumors, 14,20 while its presence in mesenchymal neoplasm is inconstant and rarely has a prognostic relevance. 11,18,23,25 Mitotic index and MIB-1 labeling index of PWTs were similar to what has been reported, 4,47 and a statistical association with the expression of GFs was not identified. This result, although deceiving, is not surprising, since neoplastic cell proliferation rate is likely the result of the interaction among several GFs, GF receptors, and other cell cycle regulators, but the number of cases included in this study did not allow the evaluation of association patterns of multiple GFs.…”

Kinome Profiling of NF1-Related MPNSTs in Response to Kinase Inhibition and Doxorubicin Reveals Therapeutic Vulnerabilities

“…In both capmatinib-and trametinib-treated tumors, inflammatory signaling was present at the 4-h time point, whereas kinase signaling associated with proliferation and invasion dominated at 2 days and 21 days. Inflammation has not been widely studied in MPNSTs; however, it is a key determinant of neurofibroma progression and Schwann cell homeostasis [40][41][42]. Based on our data, all treatments were associated with an initial inflammatory response directly mediated by the kinome.…”

Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways

“…Repetitive exposure to Cr(VI) results in persistent inflammation, and such an inflammatory microenvironment can further promote lung carcinogenesis (Beaver et al , 2009a; Beaver et al , 2009b). Cyclooxygenase-2 (COX-2) is a key enzyme in the conversion of arachidonic acid to prostanoids, and its activation is associated with inflammation and carcinogenesis (Hakozaki et al , 2014). Elevated COX-2 expression has been demonstrated in Cr(VI)-exposed cultured cells (Zuo et al , 2012; Son et al , 2013).…”