Changes in antitumor response in C57BL/6J-Min/+ mice during long-term administration of a selective cyclooxygenase-2 inhibitor

Adelaide M. Carothers, Amy E. Moran, Nancy L. Cho, Mark Redston, Monica M. Bertagnolli

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Selective cyclooxygenase-2 (COX-2) inhibitors are widely prescribed for severe arthritis and are currently under study in human chemoprevention trials. Recently, long-term use of these agents has come under scrutiny due to reports of treatment-associated cardiovascular toxicity. On short-term administration, the selective COX-2 inhibitor celecoxib inhibits adenoma growth in animal tumor models, including the C57BL/6J-Min/+ (Min/+) mouse. With uninterrupted long-term celecoxib administration, intestinal tumors in Min/+ mice initially regressed and then recurred to levels comparable with untreated controls. Celecoxib treatment initially suppressed COX-2 and prostaglandin E2 (PGE 2) expression, but long-term use produced significantly higher levels of these molecules and reactivated PGE2-associated growth factor signaling pathways in tumor and normal tissues. These results indicate that COX-2 is an important chemoprevention target and that inhibition of this enzyme alters a paracrine enterocyte regulatory pathway. Chronic uninterrupted celecoxib treatment, however, induces untoward effects that enhance early progression events in intestinal tumorigenesis and may contribute to treatment toxicity.

Original languageEnglish (US)
Pages (from-to)6432-6438
Number of pages7
JournalCancer Research
Volume66
Issue number12
DOIs
StatePublished - Jun 15 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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