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

Neoplasia. Sep-Oct 2001;3(5):428-36. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Division / drug effects*
  • Cell Division / physiology
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / pathology
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / therapeutic use*
  • Flow Cytometry
  • Gene Expression Profiling
  • Humans
  • Immunoblotting
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / genetics
  • Membrane Proteins
  • Mice
  • Mice, Nude
  • Mitotic Index
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Pyrazoles / therapeutic use*
  • RNA / analysis
  • RNA / metabolism
  • Tetrazolium Salts
  • Thiazoles
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Substances

  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Pyrazoles
  • Tetrazolium Salts
  • Thiazoles
  • 1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole
  • RNA
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • thiazolyl blue