Intra-tumor injection of an angiogenesis inhibitor, TNP-470, in rabbits bearing VX2 carcinoma of the tongue.
A semi-synthetic analogue of fumagillin, TNP-470, has been shown to be a potent angiogenesis inhibitor. In this study, we evaluated the anti-tumor efficacy of TNP-470 on rabbits bearing VX2 carcinoma of the tongue, by comparison of topical, intra-tumor (i.t.) injection with systemic, intra-venous (i.v.) administration. The i.t. injection of the angiogenesis inhibitor produced much stronger anti-tumor effects, and almost complete tumor regression was achieved at doses of 10 mg/kg or 20 mg/kg. TNP-470 injected intra-tumorally significantly reduced expression of proliferating cell nuclear antigen (PCNA) and microvessel density in the VX2 carcinoma of the tongue. TNP-470 also halted the tumor-associated neovascularization in the rabbit cornea assay. These data suggest that i.t. injection of TNP-470 effectively inhibits tumor angiogenesis and disrupts microvasculature development, which may suppress tumor growth. In conclusion, the i.t. injection of TNP-470 provided remarkable anti-tumor effects on the VX2 carcinoma of the tongue and is expected to have promising therapeutic uses for oral cancer.
Matsumoto
K
K
First Department of Oral and Maxillofacial Surgery, Fukuoka Dental College, Japan.
Ninomiya
Y
Y
Inoue
M
M
Tomioka
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D002277:Carcinoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D003316:Corneal Diseases / Q000188:drug therapy / Q000473:pathology; D003510:Cyclohexanes; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005134:Eye Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D015552:Injections, Intralesional; D008297:Male; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011817:Rabbits; D012717:Sesquiterpenes / Q000008:administration & dosage*; D013997:Time Factors; D014062:Tongue Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol