Multiple drug resistance phenotype of human endothelial cells induced by vascular endothelial growth factor 165

AIM: To investigate the effect of vascular endothelial growth factor 165 (V EGF(165)) on sensitivity of endothelial cells to anticancer drugs. METHODS: Human dermal microvessel endothelial cells (HDMEC) were incubated with ant icancer drugs in the presence of VEGF(165). Survival of endothelial cells w as assayed by NM method. DNA fragments of apoptosis were detected by agaros e electrophoresis. Potential mechanisms underlying the effect of VEGF(165) on endothelial cells were investigated with RT-PCR and Western blot analysi s. RESULTS.. VEGF(165) induced the multidrug resistance phenotype of HDMEC to a wide variety of anticancer drugs such as epirubicin, cisplatin, etopos ide, mytomycin C, vincristine, CPT-11, and taxol in vitro. This protective effect was partly due to the up-regulation of lung drug resistance protein (LRP) and multidrug resistance-associated protein (MRP), as well as the dow n-regulation of Bax protein induced by VEGF(165). CONCLUSION: VEGF(165) ind uced multidrug resistance phenotype of endothelial cells, which implicated the anti-angiogenic effect of anticancer drugs might depend on microenviron ment of tumors in vivo.