Antiangiogenic therapy targeting the tyrosine kinase receptor for vascularendothelial growth factor receptor inhibits the growth of colon cancer liver metastasis and induces tumor and endothelial cell apoptosis

Increased vascular endothelial growth factor (VEGF) expression is associate d with colon cancer metastases. We hypothesized that inhibition of VEGF rec eptor activity could inhibit colon cancer liver metastases. BALB/c mice und erwent splenic injection with CT-26 colon cancer cells to generate metastas es, Mice received daily i.p. injections of vehicle, tyrosine kinase inhibit or for Flk-1/KDR (SU5416) or tyrosine kinase inhibitor for VEGF, basic fibr oblast growth factor, and platelet-derived growth factor receptors (SU6668) . SU5416 and SU6668 respectively inhibited metastases (48.1% and 55.3%), mi crovessel formation (42.0% and 36.2%), and cell proliferation (24.4% and 27 .3%) and increased tumor cell (by 2.6- and 4.3-fold) and endothelial cell ( by 18.6- and 81.4-fold) apoptosis (P < 0.001). VEGF receptor inhibitors inc reased endothelial cell apoptosis, suggesting that VEGF may serve as an end othelial survival factor.