Anticancer Effect of COX-2 Inhibitor DuP-697 Alone and in Combination with Tyrosine Kinase Inhibitor (E7080) on Colon Cancer Cell Lines

Abstract

Colorectal cancer remains one of the most common types of cancer and a leading cause of cancer deathworldwide. In this study, we aimed to investigate effects of DuP-697, an irreversible selective inhibitor of COX-2 on colorectal cancer cells alone and in combination with a promising new multi-targeted kinase inhibitorE7080. The HT29 colorectal cancer cell line was used. Real time cell analysis (xCELLigence system) wasconducted to determine effects on colorectal cell proliferation, angiogenesis was assessed with a chorioallantoicmembrane model and apoptosis was determined with annexin V staining. We found that DuP-697 alone exertedantiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. For the antiproliferativeeffect the half maximum inhibition concentration (IC50) was 4.28510-8 mol/L. Antiangiogenic scores were 1.2,0.8 and 0.5 for 100, 10 and 1 nmol/L DuP-697 concentrations, respectively. We detected apoptosis in 52% ofHT29 colorectal cancer cells after administration of 100 nmol/L DuP-697. Also in combination with the thyrosinekinase inhibitor E7080 strong antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancercells were observed. This study indicates that DuP-697 may be a promising agent in the treatment of colorectalcancer. Additionally the increased effects observed in the combination with thyrosine kinase inhibitor give thepossibility to use lower doses of DuP-697 and E7080 which can avoid and/or minimize side effects.