A Cyclooxygenase-2 Inhibitor (SC-58125) Blocks Growth of Established Human Colon Cancer Xenografts

• 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
• Subjects: colorectal cancer; COX-2; cancer prevention; prostaglandins; cell cycle arrest
• Online Access: http://www.sciencedirect.com/science/article/pii/S1476558601800567

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.