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.
Miura
Shin-ichiro
S
Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-Ku, Fukuoka, 814-0180, Japan. miuras@cis.fukuoka-u.ac.jp
Emoto
Makoto
M
Matsuo
Yoshino
Y
Kawarabayashi
Tatsuhiko
T
Saku
Keijiro
K
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D002296:Carcinosarcoma / Q000098:blood supply*; D049109:Cell Proliferation / Q000187:drug effects; D003510:Cyclohexanes; D004357:Drug Synergism; D005260:Female; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D048670:MAP Kinase Kinase 4; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000098:blood supply*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012717:Sesquiterpenes; D042461:Vascular Endothelial Growth Factor A; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000077609:O-(Chloroacetylcarbamoyl)fumagillol