The inhibitory effects of TNP470 on tumour growth of head and neck carcinoma cell producing interleukin-8.
The anti-tumour effect of the angiogenic inhibitor TNP470, sigma-(chloro-acetyl-carbamoyl) fumagillol, a synthetic analogue of fumagillin, was studied in vitro and in vivo using KB cells, one of the human head and neck carcinoma cell lines that produce interleukin(IL)-8. In the in vitro study, the combination treatment of TNP470 and anti-IL-8 antibody significantly reduced the proliferation of KB cells. In the in vivo studies, TNP470 administration by any route (intratumoral: i.t., intraperitoneal: i.p., intravenous: i.v.) reduced the tumour volume significantly, compared to the control group. Among the groups administered TNP470, the anti-tumour effect was strongest in the it group. Furthermore, the concurrent treatment of anti-IL-8 antibody and TNP470 also maximally reduced the tumour volume. The combination therapy of TNP470 and anti-IL-8 antibody was very effective. These results suggest that combination therapy of TNP470 and anti-IL-8 antibody could be beneficial for solid tumours, such as head and neck cancer.
Kawano
T
T
Research Institute, Kanagawa Cancer Center, Yokohama, Japan.
Yanoma
S
S
Nishimura
G
G
Tsukuda
M
M
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003131:Combined Modality Therapy; D003510:Cyclohexanes; D003864:Depression, Chemical; D005434:Flow Cytometry; D006801:Humans; D015552:Injections, Intralesional; D016209:Interleukin-8 / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009368:Neoplasm Transplantation; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D003510:Cyclohexanes; D016209:Interleukin-8; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol