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

Autor: Michiro Yanagisawa, Takahiro Tajino, Hitoshi Yamada, Michiyuki Hakozaki, Masafumi Abe, Jun Nishida, Takashi Tsuchiya, Hiroshi Hojo, Hiroyuki Nagasawa, Shinichi Konno, Shinichi Kikuchi, Akira Ogose
Rok vydání: 2014
Předmět:
Male
Pathology
Cancer Treatment
lcsh:Medicine
Apoptosis
Kaplan-Meier Estimate
medicine.disease_cause
Nerve Sheath Neoplasms
Drug Discovery
Basic Cancer Research
lcsh:Science
Neurological Tumors
Caspase
Aged
80 and over
Multidisciplinary
biology
Chemistry
Soft tissue sarcoma
Middle Aged
Caspase Inhibitors
Immunohistochemistry
Oncology
Caspases
Medicine
Oncology Agents
Female
medicine.symptom
Immunohistochemical Analysis
Nerve sheath neoplasm
Research Article
Adult
Drugs and Devices
medicine.medical_specialty
Drug Research and Development
Adolescent
Inflammation
Malignant peripheral nerve sheath tumor
DNA Fragmentation
Young Adult
Cell Line
Tumor
medicine
Humans
Cell Shape
Aged
Cyclooxygenase 2 Inhibitors
lcsh:R
Cancers and Neoplasms
Chemotherapy and Drug Treatment
medicine.disease
Enzyme Activation
Cyclooxygenase 2
Multivariate Analysis
Immunologic Techniques
biology.protein
Etodolac
Clinical Immunology
lcsh:Q
Cyclooxygenase
Carcinogenesis
Zdroj: PLoS ONE, Vol 9, Iss 2, p e88035 (2014)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0088035
Popis: 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.
Databáze: OpenAIRE
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