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 agent, were investigated using our established liver-metastasizing gastric 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 given saline solution, a group receiving 15 mg/kg TNP-470, a group receiving 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 intrasplenic injection, and MMC 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 developed in 6 of 11 mice (55%) receiving MMC. In contrast, liver metastasis developed in 4 of 8 mice (50%) receiving 15 mg/kg TNP-470, and in 0 of 14 mice (0%) receiving 30 mg/kg TNP-470. However, TNP-470 had no effect on the tumor growth. These results indicate that the angiogenesis inhibitor TNP-470 has a strong inhibitory activity against in vivo liver metastasis of human gastric carcinoma.