Inhibitory Effect of the Angiogenesis Inhibitor FR-118487 on Liver Metastasis in a Rabbit Colon Cancer Model by Continuous Intraarterial Infusion

Michiaki Ueoka

Department of Surgery II, Okayama University School of Medicine

The antimetastatic effect of FR-118487 was investigated in rabbit colon cancer models. Spontaneous liver metastases were induced by VX2 tumor cell implantations into ascending colonic walls. FR-118487 was administered for one week at a dose of 1 mg/kg/day via the hepatic artery (IA group) or the portal vein (IP group) after resection of the primary lesion. The number of metastatic foci tended to be less in the IA and IP groups than in the control group. The weight of metastatic foci were significantly less in the IA and IP groups than in the control group (p<0.01 and p<0.05, respectively). Immunohistological study by factor VIII related antigen staining showed that microvessel density of metastatic foci were significantly less in the IA and IP groups than in the control group (p<0.05). The continuous infusion of FR-118487 suppressed liver metastasis by inhibiting angiogenesis without any adverse effects. The incidence of liver metastasis was 40%, 71% and 100%, in the IA, IP and control groups, respectively. These results suggest that delivery of FR-118487 is more effective via the IA route than the IP route for preventing liver metastasis after resection of primary lesion.

Key words
angiogenesis inhibitor FR-118487, liver metastasis from colon cancer, continuous intraarterial infusion, factor VIII related antigen, microvessel density

Reprint requests
Michiaki Ueoka Department of Surgery II, Okayama University School of Medicine 2-5-1 Shikata-cho, Okayama, 700-0914 JAPAN

Accepted
December 9, 1998

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