Chemopreventative celecoxib fails to prevent schwannoma formation or sensorineural hearing loss in genetically engineered murine model of neurofibromatosis type 2

被引：7

作者：

Wahle, Benjamin M. ^{[1
,2
]}

Hawley, Eric T. ^{[1
]}

He, Yongzheng ^{[1
]}

Smith, Abbi E. ^{[1
]}

Yuan, Jin ^{[1
]}

Masters, Andi R. ^{[3
]}

Jones, David R. ^{[3
]}

Gehlhausen, Jeffrey R. ^{[1
]}

Park, Su-Jung ^{[1
]}

Conway, Simon J. ^{[1
]}

Clapp, D. Wade ^{[1
]}

Yates, Charles W. ^{[1
,2
]}

机构：

[1] Indiana Univ Sch Med, Dept Pediat, Wells Ctr Pediat Res, Indianapolis, IN 46202 USA

[2] Indiana Univ Sch Med, Dept Otolaryngol Head & Neck Surg, Indianapolis, IN 46202 USA

[3] Indiana Univ, Simon Canc Ctr, Clin Pharmacol Analyt Core, Indianapolis, IN 46204 USA

来源：

ONCOTARGET | 2018年 / 9卷 / 01期

关键词：

neurofibromatosis type 2; vestibular schwannoma; cyclooxygenase; 2; non-steroidal anti-inflammatory agents; transgenic mice; CELL-SURVIVAL; PROGRESSION; COMBINATION; EXPRESSION; ASPIRIN;

D O I：

10.18632/oncotarget.22002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Mutations in the tumor suppressor gene NF2 lead to Neurofibromatosis type 2 (NF2), a tumor predisposition syndrome characterized by the development of schwannomas, including bilateral vestibular schwannomas with complete penetrance. Recent work has implicated the importance of COX-2 in schwannoma growth. Using a genetically engineered murine model of NF2, we demonstrate that selective inhibition of COX-2 with celecoxib fails to prevent the spontaneous development of schwannomas or sensorineural hearing loss in vivo, despite elevated expression levels of COX-2 in Nf2-deficient tumor tissue. These results suggest that COX-2 is nonessential to schwannomagenesis and that the proposed tumor suppressive effects of NSAIDs on schwannomas may occur through COX-2 independent mechanisms.

引用

页码：718 / 725

页数：8

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