Comparison of the inhibitory effect of the angiogenesis inhibitor, TNP‐470, and mitomycin c on the growth and liver metastasis of human colon cancer

Angiogenesis inhibitors have attracted considerable interest. 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 a xenotrans‐planted human colon cancer, TK‐4. Suturing of small pieces of TK‐4 tumors to the cecal wall in nude mice (orthotopic transplantation) induced liver metastasis. Mice were randomly divided into 3 groups; a control group given saline solution, a group receiving TNP‐470 and a group receiving MMC. TNP‐470 was given s.c. on alternate days for 5 weeks from day 10 after cecal transplantation and MMC was administered intraperitoneally (i.p.) once a week from day 10 after cecal transplantation. MMC significantly inhibited cecal tumor growth. In the control group, liver metastases developed in 9 out of 10 mice, including 3 with more than 20 metastatic foci. Liver metastasis also developed in 8 out of 10 mice receiving MMC, 2 of which had many metastases. In contrast, liver metastasis developed in only 2 out of 8 mice in the TNP‐470 group and neither of these animals had numerous metastases. © 1995 Wiley‐Liss, Inc .