A cyclooxygenase-2 inhibitor (SC-58125) blocks growth of established human colon cancer xenografts.
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.
Williams
C S
CS
Department of Medicine, The Vanderbilt Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232-2279, USA.
Sheng
H
H
Brockman
J A
JA
Armandla
R
R
Shao
J
J
Washington
M K
MK
Elkahloun
A G
AG
DuBois
R N
RN
D000818:Animals; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000235:genetics; D008565:Membrane Proteins; D051379:Mice; D008819:Mice, Nude; D008940:Mitotic Index; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D011720:Pyrazoles / Q000627:therapeutic use*; D012313:RNA / Q000032:analysis / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D013778:Tetrazolium Salts; D013844:Thiazoles; C090859:1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole; D012313:RNA; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C022616:thiazolyl blue