Inhibition of liver metastases in rabbits by arterial infusion of angiogenesis inhibitor, TNP-470

We examined the prevention of liver metastases by arterial infusion of the angiogenesis inhibitor, TNP-470, in Japanese White Rabbits; 1.0 x 10(6) of VX2 carcinoma cells were injected into the mesenteric vein for tumor inoculation. Then the rabbits were divided into the following two groups. Group 1: 2 ml of distilled water was continuously injected into the common hepatic artery of control for 7 days. Group 2: 50 mg of TNP-470 solved in 2 ml of distilled water was continuously administered into the common hepatic artery for 7 days. On day 14, the number of metastases on each liver surface was counted. The mean number of metastases were 237.0 +/- 133.26 and 24.4 +/- 15.05 in Group 1 and 2, respectively. There was a significant difference between the two groups (p < 0.05). We found no side effects of TNP-470 such as body weight loss or liver disfunction. Microphil was injected into the common hepatic artery to observe the neovasculature. The proliferation of tumor vessels was suppressed in Group 2. We considered that arterial infusion of TNP-470 is effective to prevent liver metastases, because the blood supply to liver metastases is well developed from the hepatic artery, and TNP-470 is directly effective on the endothelium itself, and inhibits neovascularization.