In order to better understand the development of skeletal
metastases, we developed an appropriate animal model, as the natural progression of
metastases in humans cannot be studied on the cellular level. In this study, we established a new animal model which developed bone
metastasis in a bone grafted 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% of the extraskeletal bones. Using this model, the antimetastatic effect of a
polyamine synthesis inhibitor was investigated. Inhibitors of the
polyamine biosynthetic pathway have received considerable attention for their potential use in the treatment of
cancer as they are responsible for the greatly increased production of the
polyamines putrescine,
spermidine, and
spermine. A
polyamine synthesis inhibitor,
methylglyoxal-bis(cyclopentylamidinohydrazone)
MGBCP, was investigated for its inhibitory effects on bone
metastases.
MGBCP (20 mg/kg) was administered intraperitoneally every day for 4 weeks and demonstrated strong inhibitory effects on bone
metastases.
MGBCP inhibited angiogenesis in the transplanted bone and the growth of
B16 melanoma cells, thus suggesting a preventive mechanism in bone
metastasis. No remarkable adverse effects of
MGBCP were observed in any animal throughout the experimental period. Our results indicate that
MGBCP has a strong potential for use as an anti-metastatic
drug.