A cyclooxygenase-2 inhibitor (SC-58125) blocks growth of established human colon cancer xenografts

Christopher S. Williams, Sheng Hongmiao, Jeffrey A. Brockman, Radhika Armandla, Jinyi Shao, M. Kay Washington, Abdel G. Elkahloun, Raymond N. Dubois

    Research output: Contribution to journalArticle

    33 Scopus citations

    Abstract

    Selective COX-2 inhibitors reduce adenoma formation and cancer progression in rodent models of colorectal cancer. To assess the therapeutic activity of selective COX-2 inhibitors, we tested the effect of SC-58125 treatment on the growth of human colon carcinoma cells in nude mice. Delaying treatment by 2, 4, or 7 weeks following implantation of the carcinoma cells resulted in a significant inhibition of tumor growth. Furthermore, short-term (48 hours) treatment with SC-58125 was sufficient to attenuate tumor growth for up to 15 days. SC-58125 treatment did not alter the rate at which cells underwent apoptosis, but did result in a delayed progression through the cell cycle at the G2/M transition. Accordingly, p34cdc2 protein levels and activity were decreased following SC-58125 treatment. We conclude that SC-58125 primarily exerts a cytostatic effect in vivo, which is likely to be mediated through inhibition of progression through the G2/M phase of the cell cycle.

    Original languageEnglish (US)
    Pages (from-to)428-436
    Number of pages9
    JournalNeoplasia
    Volume3
    Issue number5
    DOIs
    StatePublished - 2001

    Keywords

    • COX-2
    • Cancer prevention
    • Cell cycle arrest
    • Colorectal cancer
    • Prostaglandins

    ASJC Scopus subject areas

    • Cancer Research

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  • Cite this

    Williams, C. S., Hongmiao, S., Brockman, J. A., Armandla, R., Shao, J., Washington, M. K., Elkahloun, A. G., & Dubois, R. N. (2001). A cyclooxygenase-2 inhibitor (SC-58125) blocks growth of established human colon cancer xenografts. Neoplasia, 3(5), 428-436. https://doi.org/10.1038/sj.neo.7900177