Bevacizumab Efficiently Inhibits VEGF-Associated Cellular Processes in Equine Umbilical Vein Endothelial Cells: An In Vitro Characterization

SIMPLE SUMMARY: Angiogenesis, the sprouting of new capillaries from existing vessels, plays a crucial role in various physiological processes. Pathological vascularization, as seen in, e.g., cancer, musculoskeletal diseases, or ocular disorders, eventually causes tissue and organ dysfunctions. Vascular endothelial growth factor A (VEGF-A) and its receptors are known to play a key role in angiogenesis; therefore, targeting the VEGF pathway represents one of the main areas of human cancer research in recent years. So far, anti-VEGF treatment in horses has not been investigated. In this study, the effect of bevacizumab, the most widespread anti-VEGF agent, on an equine cell line harvested from umbilical cords was investigated. Bevacizumab efficiently inhibited various cellular processes associated with angiogenesis and could therefore be a promising therapeutic approach in vascular-driven diseases in horses. ABSTRACT: Anti-VEGF agents were found to have clinical implications for the successful treatment of vascular-driven diseases in humans. In this study, a detailed biological characterization of bevacizumab in a variety of in vitro assays was carried out to determine the effect of bevacizumab on equine umbilical vein endothelial cells (EqUVEC). EqUVECs were harvested from umbilical cords of clinically healthy horses and exposed to different concentrations (1, 2, 4, 6, 8 mg/mL) of bevacizumab (Avastin(®)). Assays concerning the drug’s safety (cell viability and proliferation assay) and efficacy (cell tube formation assay, cell migration assay, and Vascular endothelial growth factor (VEGF) expression) were carried out reflecting multiple cellular processes. Bevacizumab significantly decreased VEGF expression at all concentrations over a 72 h period. No cytotoxic effect of bevacizumab on EqUVECs was observed at concentrations of 4 mg/mL bevacizumab or lower. Incubated endothelial cells showed delayed tube formation and bevacizumab efficiently inhibited cell migration in a dose-dependent manner. Bevacizumab potently inhibits VEGF-induced cellular processes and could be a promising therapeutic approach in vascular-driven diseases in horses.