INHIBITION OF LIVER METASTASIS OF HUMAN GASTRIC-CARCINOMA BY ANGIOGENESIS INHIBITOR TNP-470

The anti-tumor and anti-metastatic effects of TNP-470, an angiogenesis inhibitor, and mitomycin C (MMC), a representative anti-neoplastic ag ent, were investigated using our established liver-metastasizing gastr ic carcinoma line, AZ-H5c. AZ-H5c was injected into the spleen of nude mice which had been randomly divided into 4 groups; a control group g iven saline solution, a group receiving 15 mg/kg TNP-470, a group rece iving 30 mg/kg TNP-470 and a group receiving 2 mg/kg MMC. TNP-470 was given s.c. on alternate days for 5 weeks from day 10 after intraspleni c injection, and MR IC was administered intraperitoneally (i.p.) once a week from day 10 after intrasplenic injection. In the control group, liver metastasis developed in 13 of 16 mice (81%). Liver metastasis d eveloped in 6 of 11 mice (55%) receiving MMC. In contrast, liver metas tasis developed in 4 of 8 mice (50%) receiving 15 mg/kg TNP-470, and i n 0 of 14 mice (0%) receiving 30 mg/kg TNP-470. However, TNP-470 had n o effect on the tumor growth. These results indicate that the angiogen esis inhibitor TNP-470 has a strong inhibitory activity against in viv o liver metastasis of human gastric carcinoma.