Carcinosarcoma-induced endothelial cells tube formation through KDR/Flk-1 is blocked by TNP-470

We evaluated the usefulness of TNP-470 as an anti-cancer agent on a human uterine carcinosarcoma cell line (FU-MMT-1). FU-MMT-1 induced human arterial endothelial cell (HAEC) tube formation on an in vitro co-cultured model of FU-MMT-1 and HAECs on a matrix gel, and was blocked by vascular endothelial growth factor (VEGF)-2 receptor (KDR/Flk-1) tyrosine kinase inhibitor. Lower concentration of TNP-470 inhibited the tube formation. Cell proliferation of FU-MMT-1 but not HAEC was inhibited by lower concentration of TNP-470. In addition, lower concentration of TNP-470 blocked VEGF production on FU-MMT-1. Our results suggest that TNP-470 directly inhibited FU-MMT-1 but not HAEC growth accompanied with the inhibition of VEGF production, subsequently induced anti-angiogenesis on HAEC.