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

  • Neoplasia. 2001 Sep-Oct;3(5):428-36. doi: 10.1038/sj.neo.7900177.
C S Williams  1 ,  H Sheng ,  J A Brockman ,  R Armandla ,  J Shao ,  M K Washington ,  A G Elkahloun ,  R N DuBois
Affiliations
  • 1. Department of Medicine, The Vanderbilt Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232-2279, USA.
PMID: 11687954 DOI: 10.1038/sj.neo.7900177
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 G(2)/M transition. Accordingly, p34(cdc2) 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 G(2)/M phase of the cell cycle.

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