Anti-tumor effects of bevacizumab in combination with paclitaxel on head and neck squamous cell carcinoma.
Human tumors are dependent on angiogenesis for growth, and the vascular endothelial growth factor (VEGF) is a major regulator of this process. Bevacizumab (Avastin), a monoclonal antibody directed against VEGF, has shown promise in treating a variety of cancers. In this study, we first examined the anti-tumor effects of bevacizumab on head and neck squamous cell carcinoma (HNSCC). Then we examined the effects of bevacizumab combined with paclitaxel, a chemotherapeutic agent, in HNSCC. This is the first demonstration of the anti-tumor effects of bevacizumab on HNSCC. In vitro, bevacizumab did not show any antiproliferative effects against the HNSCC cell lines. However, in vivo, bevacizumab showed dramatic anti-tumor effects against HNSCC tumor xenografts in mice. In addition, treatment with a bevacizumab-paclitaxel combination resulted in a remarkable inhibition of the HNSCC tumor xenografts, compared to the effects of each agent separately. A decreased blood vessel density and an increased apoptotic index were seen in the shrunken tumors. These results suggest that bevacizumab in combination with paclitaxel could have useful clinical application in HNSCC.
Fujita
Kyoko
K
Department of Biology and Function in Head and Neck, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan. t056043b@yokohama-cu.ac.jp
Sano
Daisuke
D
Kimura
Machiko
M
Yamashita
Yukiko
Y
Kawakami
Mariko
M
Ishiguro
Yukari
Y
Nishimura
Goshi
G
Matsuda
Hideki
H
Tsukuda
Mamoru
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D000068258:Bevacizumab; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008833:Microcirculation; D009389:Neovascularization, Pathologic / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000637:transplantation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D017239:Paclitaxel