Antitumor effects of ZD6474 on head and neck squamous cell carcinoma.
Angiogenesis is required for tumor growth and metastasis and, therefore, represents a target for cancer treatment. While many factors have been implicated in promoting angiogenesis, vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis. ZD6474 is a potent VEGF receptor-2 (VEGFR-2) tyrosine kinase inhibitor which also has activity against the epidermal growth factor receptor (EGFR) tyrosine kinase. The purpose of this study was to investigate the sensitivity of head and neck squamous cell carcinoma (HNSCC) cell lines to ZD6474, and to evaluate its antitumor efficacy on HNSCC xenografts. This is the first demonstration of antitumor effects of ZD6474 on HNSCC. In vitro ZD6474 displayed antiproliferative effects on HNSCC cells and inhibition of VEGFR-2 and EGFR pathways. In vivo ZD6474 displayed antitumor activity, induced apoptosis and antiangiogenic activity on nude mice bearing an established xenograft of YCU-H891 cells. These results suggest that ZD6474 has the potential to inhibit two key pathways in tumor growth via inhibition of VEGF-dependent tumor angiogenesis and via inhibition of EGFR-dependent tumor cell proliferation.
Sano
Daisuke
D
Department of Biology and Function in the Head and Neck, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan. t046028d@yokohama-cu.ac.jp
Kawakami
Mariko
M
Fujita
Kyoko
K
Kimura
Machiko
M
Yamashita
Yukiko
Y
Ishiguro
Yukari
Y
Nishimura
Goshi
G
Matsuda
Hideki
H
Tsukuda
Mamoru
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D008956:Models, Chemical; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D010880:Piperidines / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*
D000970:Antineoplastic Agents; D010880:Piperidines; D011799:Quinazolines; C452423:vandetanib