Synergy between Celecoxib and Radiotherapy Results from Inhibition of Cyclooxygenase-2-Derived Prostaglandin E2, a Survival Factor for Tumor and Associated Vasculature

Thomas W. Davis, Janet M. O'Neal, Mark D. Pagel, Ben S. Zweifel, Pramod P. Mehta, Deborah M. Heuvelman, Jaime L. Masferrer

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Previous work has demonstrated that selective cyclooxygenase-2 (COX-2) inhibitors can act synergistically with radiotherapy to improve tumor debulking and control in preclinical models. The underlying mechanism of this remarkable activity has not yet been determined. Here, we report that radiation can elevate intratumoral levels of COX-2 protein and its products, particularly prostaglandin E2 (PGE2). Furthermore, inhibition of COX-2 activity or neutralization of PGE2 activity enhances radiotherapy even in tumors where COX-2 expression is restricted to the tumor neovasculature. Direct assessment of vascular function by direct contrast enhancement-magnetic resonance imaging showed that the combination of radiation and celecoxib lead to enhanced vascular permeability. These observations suggest that an important mechanism of celecoxib-induced radiosensitization involves inhibition of COX-2-derived PGE2, thus removing a survival factor for the tumor and its vasculature.

Original languageEnglish (US)
Pages (from-to)279-285
Number of pages7
JournalCancer Research
Volume64
Issue number1
DOIs
StatePublished - Jan 1 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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