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 treatmen...

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Bibliographic Details
Main Authors: Christopher S. Williams, Hongmiao Sheng, Jeffrey A. Brockman, Radhika Armandla, Jinyi Shao, M. Kay Washington, Abdel G. Elkahloun, Raymond N. Dubois
Format: Article
Language:English
Published: Elsevier 2001-01-01
Series:Neoplasia: An International Journal for Oncology Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S1476558601800567
Description
Summary: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.
ISSN:1476-5586
1522-8002