Treatment of Human Metastatic Transitional Cell Carcinoma of the Bladder in a Murine Model with the Anti-Vascular Endothelial Growth Factor Receptor Monoclonal Antibody DC101 and Paclitaxel

摘要: Vascular endothelial cell growth factor (VEGF) regulates angiogenesis and metastasis of bladder cancer (transitional carcinoma, TCC) through binding to VEGF receptor-2 (VEGFR-2). In this study, we evaluated whether the anti-VEGFR monoclonal antibody (Mab) DC101 in combination with paclitaxel inhibited tumorigenesis, angiogenesis, human TCC growing within athymic nude mice. vivo therapy Mab induced significant regression tumors compared either agent alone. Median weights were reduced from 601 mg untreated controls, 422 mice treated alone (P < 0.005), 361 113 that received 0.0005). Only one nine developed spontaneous lymph node after combined treatment, seven controls 0.0005), six eight 0.01), five 0.05). Combined treatment both tumor-induced neovascularity all other groups without altering expression or flk1. enhanced apoptosis tumor cells 0.005). These studies indicate DC101, which blocks VEGFR-2 function, has efficacy against TCC, especially when chemotherapeutic paclitaxel. The antitumor effect was mediated by inhibition induction apoptosis.