Cyclooxygenase-1 is overexpressed and promotes angiogenic growth factor production in ovarian cancer

Rajnish A. Gupta, Lovella V. Tejada, Beverly J. Tong, Sanjoy K. Das, Jason D. Morrow, Sudhansu K. Dey, Raymond N. DuBois

    Research output: Contribution to journalArticlepeer-review

    197 Scopus citations

    Abstract

    Inhibition of cyclooygenase-2 (COX-2) catalytic activity has proven successful in restricting the growth of epithelial-derived cancers in vivo. Whether COX-2 inhibitor therapy would be beneficial in the prevention and/or treatment of ovarian cancer, the most lethal gynecological malignancy worldwide, is not known. Most patients with ovarian cancer undergo cytoreductive therapy. Because many of the cytotoxic drugs used to treat ovarian cancer induce COX-2 expression, samples from patients that had not undergone cytoreductive therapy were specifically chosen for COX isoform expression analysis. A majority of specimens exhibited elevated levels of COX-1, not COX-2, mRNA, and protein compared with normal ovarian tissue. Focal regions within the tumor expressing high COX-1 also had elevated levels of pro-angiogenic proteins. Selective inhibition of COX-1, not COX-2, inhibited arachidonic acid-stimulated vascular endothelial growth factor production, which could be reversed by cotreatment with prostaglandin E2. Thus, COX-1 may contribute to carcinoma development in the ovary through stimulation of neovascularization. Clinical studies testing the efficacy of COX inhibition as adjuvant therapy for ovarian cancer may see more beneficial effects with adjuvant therapy with either a COX-1 selective or nonselective cyclooxygenase inhibitor as compared with a COX-2 selective drug.

    Original languageEnglish (US)
    Pages (from-to)906-911
    Number of pages6
    JournalCancer Research
    Volume63
    Issue number5
    StatePublished - Mar 1 2003

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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