Tyrosine kinase inhibition of multiple angiogenic growth factor receptors improves survival in mice bearing colon cancer liver metastases by inhibition of endothelial cell survival mechanisms.

摘要: Redundant mechanisms mediate colon cancer angiogenesis. Targeting multiple angiogenic factors simultaneously may improve survival of mice with metastases. BALB/c underwent splenic injection CT-26 cells to generate liver metastases and received administration either vehicle alone or a tyrosine kinase inhibitor for vascular endothelial growth factor, basic fibroblast platelet-derived factor receptors (SU6668). Mice were sacrificed when they became moribund as determined by blinded observer. In parallel experiment, groups at earlier time points better define the kinetics effect SU6668 on parameters over time. increased median 58% (P < 0.001) led progressive increase in tumor cell apoptosis that addition, pericyte vessel coverage vascularity significantly decreased treated SU6668. Based current knowledge survival, these data suggest prevent directly (vascular factor) indirectly (pericyte coverage) affecting mechanisms.