Prevention of Metastasis by a Polyamine Synthesis Inhibitor in an Animal Bone Metastasis Model

• Published in: Oncology Vol. 59; no. 1; pp. 75 - 80
• Main Authors: Wakabayashi, Hiroki, Hibasami, Hiroshige, Iida, Kohji, Satoh, Norifumi, Yamazaki, Takashi, Sonoda, Jun, Hirata, Hitoshi, Nakashima, Kunio, Uchida, Atsumasa
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.01.2000; S. Karger AG
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - pharmacology; Biological and medical sciences; Bone Neoplasms - blood supply; Bone Neoplasms - prevention & control; Bone Neoplasms - secondary; Chemotherapy; Disease Models, Animal; Diseases of the osteoarticular system; DNA Fragmentation - drug effects; Laboratory Investigation; Medical sciences; Melanoma - genetics; Mice; Mice, Inbred C57BL; Mitoguazone - analogs & derivatives; Mitoguazone - pharmacology; Neovascularization, Pathologic; Pharmacology. Drug treatments; Polyamines - antagonists & inhibitors; Tumor Cells, Cultured; Tumors of striated muscle and skeleton; Polyamine synthesis inhibitor; Animal model; Angiogenesis; Bone metastasis; Antitumor effect; Antineoplastic agent; Polyamine; Treatment efficiency; Rodentia; Diseases of the osteoarticular system; Metastasis; Experimental study; Vertebrata; Mammalia; Mouse; Animal; Bone
• ISSN: 0030-2414; 1423-0232
• DOI: 10.1159/000012141

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.