weremaintained in nudemice,were implanted Into the cecalwall of nude miceviaa smallincisionin theserosaTNP-470(20or 30mg/kaJwasgiven s-c-everyotherday from day 10 after Implantation,and the micewere

The antimetastaticeffectof a potentangiogenesisnhibiter,O-(chloro acetyl-carbamoyl)fum@gillol (TNP-470), was Investigated in nude mice implanted with human colon cancer. Small pieces of tumors from three established human colon cancer cell lines (TK.3, TK-4, and TK-9), which weremaintained in nudemice,were implanted Into the cecalwall of nude miceviaa smallincisionin theserosaTNP-470(20or 30mg/kaJwasgiven s-c-everyotherday from day 10 after Implantation,and the micewere sacrificed after 6 weeks. There was no difference in the weight of the Implanted tumors (control group: 0.45 ±0.29 g versus treated group: 0.49 ±0.27 g). An antimeta static effect of TNP.470 was clearly demonstrated in a dose-dependent manner. In the mice given 20 mg/kg TNP-470, liver metastasis developed in 3 of 10cases. In the30-mg/kggroup,metastasis developedIn only1 of 17 mice, while it developed In 22 of 32 mIce of the control group. The number of metastatic foci was significantly less In the treated groups. TNP-470 effectively prevented liver metastasis, however, but had no effect on the growth of the primary tumor. Theseresultsindicatethat the anglogenesis Inhibitor TNP-470 has a strong inhibitory activity against in vivo hepatic metastasis of human colon cancer.