Investigating the effect of vandetanib and celecoxib combination on angiogenesis

Abstract

Objective: Angiogenesis plays an important role in various physiological and pathological conditions and is essential for tumor growth and metastasis. The aim of this study was to evaluate the effect of a combination of vandetanib and celecoxib on angiogenic tube formation and its effect on angiogenic genes (MMP-2 and MMP-9) using an in vitro model of human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were cultured and verified by flow cytometry. HUVECs were then treated with vandetanib, celecoxib, and the combination of both drugs. Then, we investigated cell viability and cell apoptosis by MTT assays and flow cytometry. The process of angiogenesis was analyzed by tube formation assays, and the effect on angiogenic genes was determined by RT-qPCR. Results: HUVECs were positive for CD144 and negative for CD14. Vandetanib, celecoxib, and their combination inhibited HUVEC viability in a dose-dependent manner (p < 0.001). The rate of apoptosis was 13.1%, 9%, and 23.7% (p < 0.001) when treated with vandetanib, celecoxib, or the combination of both drugs, respectively. Vandetanib inhibited tube formation by 43.7%, celecoxib by 21%, and their combination by 77.3% (p < 0.001), respectively. RT-qPCR revealed that both vandetanib and celecoxib reduced the expression levels of MMP-2 and MMP-9, and their combination resulted in an even greater extent of reduction in expression levels (p < 0.001). Conclusion: Celecoxib enhanced the effect of vandetanib in inhibiting in vitro angiogenesis and the combination of these two drugs led to even greater extents of inhibition than vandetanib alone.