Prevention of metastasis by a polyamine synthesis inhibitor in an animal bone metastasis model

In order to better understand the development of skeletal metastases, we de veloped an appropriate animal model, as the natural progression of metastas es in humans cannot be studied on the cellular level. In this study, we est ablished a new animal model which developed bone metastasis in a bone graft ed subcutaneously. C57BL/6 mice, which had received a bone (femur or tibia) transplanted in the dorsal subcutis, were injected with B16 melanoma cells into the left heart ventricle. Metastasis was found in approximately 70% o f the extraskeletal bones. Using this model, the antimetastatic effect of a polyamine synthesis inhibitor was investigated. Inhibitors of the polyamin e biosynthetic pathway have received considerable attention for their poten tial use in the treatment of cancer as they are responsible for the greatly increased production of the polyamines putrescine, spermidine, and spermin e. A polyamine synthesis inhibitor, methylglyoxal-bis(cyclopentylamidinohyd razone) MGBCP, was investigated for its inhibitory effects on bone metastas es. MGBCP (20 mg/kg) was administered intraperitoneally every day for 4 wee ks and demonstrated strong inhibitory effects on bone metastases. MGBCP inh ibited angiogenesis in the transplanted bone and the growth of B16 melanoma cells, thus suggesting a preventive mechanism in bone metastasis. No remar kable adverse effects of MGBCP were observed in any animal throughout the e xperimental period. Our results indicate that MGBCP has a strong potential for use as an anti-metastatic drug. Copyright (C) 2000 S. Karger AG, Basel.