Anti-Angiogenic Effects of Diltiazem, Imatinib, and Bevacizumab in the CAM Assay

Angiogenesis that plays important roles in a variety of physiological processes is strictly delimited and finely tuned by a balance of pro-angiogenic and anti-angiogenic factors. Angiogenesis is essential for viability, growth, invasion and metastasis of tumors. The chorioallantoic membrane model is considered to be a valuable method for investigation of antiangiogenic effects of drugs and other substances. The aim of the present study is to investigate the anti-angiogenic effects of a calcium channel blocker (diltiazem), a tyrosine kinase inhibitor (imatinib), and a vascular endothelial growth factor inhibitor (bevacizumab) with the means of the chicken chorioallantoic membrane (CAM) model. Each drug was administered onto the chorioallantoic membrane at the concentrations of 10 -4 M, 10 -5 M, and 10 -6 M on 8th day of incubation. After 24 h, development of the blood vessels under a stereo-microscope was investigated. The evaluations were performed using a scoring system. We evaluated anti-angiogenic effects of the drugs in two ways according to their average anti-angiogenic effect and comparison of median anti-angiogenic score. These two angiogenesis evaluation techniques provided similar results to measure antiangiogenic effects of the study drugs. Bevacizumab has the strongest anti-angiogenic effect compared to the diltiazem and imatinib, and althought not reaching statistical significance imatinib has a strong anti-angiogenic effect than that of the diltiazem.