Antitumor effect of arterial administration of a medium-chain triglyceride solution of an angiogenesis inhibitor, TNP-470, in rabbits bearing VX-2 carcinoma.
Using rabbits bearing VX-2 carcinoma on the inner side of the leg, we examined the antitumor activity of a medium-chain triglyceride (MCT) solution of an angiogenesis inhibitor, TNP-470 (AGM-1470, 6-O-(N-chloroacetylcarbamoyl)-fumagillol), following administration into the femoral artery feeding the tumor. The MCT solution of TNP-470 (1 and 5 mg) strongly suppressed tumor growth following a single intra-arterial (i.a.) injection 2 or 3 weeks after tumor inoculation. Moreover, remarkable regression of well-developed tumors, those 4 weeks after inoculation, was obtained by i.a. injection of the MCT solution containing 20 mg of TNP-470 without any influence on body weight. The antitumor effects were potentiated by coadministration of doxorubicin or mitomycin C (MMC) in the solution or microspheres containing MMC. In a shell-less chorioallantoic membrane (CAM) assay, angiogenesis was inhibited when a droplet of the MCT solution containing 25 micrograms of TNP-470 was placed on the CAM for 2 days, suggesting that the prolonged antitumor effect resulted from the inhibition of tumor neovascularization by sustained drug release from the preparation. These results indicate that i.a. injection of the MCT solution of TNP-470 is promising for treating well-developed tumors.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002210:Caprylates / Q000008:administration & dosage; D002277:Carcinoma / Q000098:blood supply* / Q000188:drug therapy*; D002626:Chemistry, Pharmaceutical; D003510:Cyclohexanes; D003652:Decanoic Acids / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D007269:Injections, Intra-Arterial; D019344:Lactic Acid; D008297:Male; D016685:Mitomycin / Q000008:administration & dosage; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage; D011817:Rabbits; D012717:Sesquiterpenes / Q000008:administration & dosage*; D012996:Solutions; D014280:Triglycerides / Q000008:administration & dosage*
D000903:Antibiotics, Antineoplastic; D002210:Caprylates; D003510:Cyclohexanes; D003652:Decanoic Acids; D011108:Polymers; D012717:Sesquiterpenes; D012996:Solutions; D014280:Triglycerides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016685:Mitomycin; D004317:Doxorubicin; C031492:octanoic acid; D000077609:O-(Chloroacetylcarbamoyl)fumagillol