Antitumor Effect of the Angiogenesis Inhibitor, TNP470, on Squamous Cell Carcinoma Cells in Head and Neck Cancer

• Published in: Nippon Jibi Inkoka Gakkai Kaiho Vol. 103; no. 7; pp. 821 - 828
• Main Authors: Kawano, Toshiro, Furukawa, Shigeru, Matsuda, Hideki, Takahashi, Masahiro, Endo, Ryo, Inoue, Maki, Nishimura, Goshi, Tsukuda, Mamoru
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Oto-Rhino-Laryngological Society of Japan, Inc 2000
• Subjects: Angiogenesis Inhibitors - administration & dosage; Animals; Antibodies, Monoclonal - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; antitumor effects; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - pathology; Cisplatin - administration & dosage; Cyclohexanes; head and neck; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - pathology; Humans; interleukin-8; Interleukin-8 - biosynthesis; Interleukin-8 - immunology; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; O-(Chloroacetylcarbamoyl)fumagillol; Sesquiterpenes - administration & dosage; squamous cell carcinoma; TNP470; Tumor Cells, Cultured
• ISSN: 0030-6622; 1883-0854
• DOI: 10.3950/jibiinkoka.103.821

The antitumor effect of the angiogenesis inhibitor TNP470, O-(chloro-acetyl-carbamoyl) fumagillol, a synthetic analogue of fumagillin, was studied in vitro and in vivo on, cell line KB which produced interleukin (IL)-8. In vitro, TNP470 reduced the production of IL-8 from KB cells, the same as anti-IL-8 antibody (Ab.) The combination of anti-IL-8 Ab(10μg/ml) and TNP470 (10ng/ml) significantly inhibited the proliferation of KB cells, compared to no treatment (p<0.05). Proliferation of KB cells was also significantly more suppressed by simultaneous treatment of cisplatin and TNP470 (1mg/ml), than cisplatin alone. The in vivo antitumor effect of TNP470 was studied using anti-IL-8 Ab, anti-vascular endothel growth factor (VEGF) Ab, and TNP470, in administered by different routes, i.e., intratumoral (i.t.), intraperitoneal (i.p.), and intravenous. TNP470 (10mg/ml) showed an antitumor effect, and intratumoral administration of TNP470 was the most effective route. Combined administration of anti-IL-8 Ab (i.p.) and TNP470 (i.t.) reduced tumor volume more than anti-IL-8 Ab alone did. These results suggest that the combination of TNP470, cisplatin, and anti-IL-8 Ab could be a beneficial treatment for solid tumors of the head and neck.