The combination of Jun N-terminal kinase inhibitor and TNP-470 blocks carcinosarcoma-induced endothelial cell tube formation in a synergistic manner

We assessed the usefulness of Jun N-terminal kinase inhibitor (JNK-I) as an anti-angiogenic agent against a human uterine carcinosarcoma cell line (FU-MMT-1). JNK-I blocked FU-MMT-1-induced human arterial endothelial cell (HAEC) tube formation in an in vitro co-culture model. Cell proliferation of FU-MMT-1 or HAEC was inhibited by JNK-I. In addition, JNK-I blocked matrix metalloproteinase production but not vascular endothelial growth factor (VEGF) secretion in HAECs. Although low concentrations of JNK-I or TNP-470, an anti-cancer agent, did not separately block FU-MMT-1-induced tube formation, such tube formation was blocked by the combination of low concentrations of JNK-I and TNP-470 because TNP-470 blocked VEGF production, suggesting that JNK-I and TNP-470 had a synergistic effect and might be effective in patients with carcinosarcoma.