Antitumour effect of a synthetic analogue of fumagillin on murine renal carcinoma

Objective To evaluate the antitumour effect of an angio-inhibitory drug, a synthetic analogue of fumagillin (TNP-470), on murine renal carcinoma (Renca) in vivo and in vitro. Materials and methods The effect of TNP-470 on the growth of Renca cells in vitro was measured by angio-genesis assay and cell counting with dye exclusion. In the angiogenesis assay, Renca cells were injected intra-dermally and the number of blood vessels orientated towards the tumours was counted 3 days after tumour inoculation. To examine the effect of TNP-470 on the subcutaneous tumour growth and lung metastasis of Renca, Renca cells were injected subcutaneously or intravenously in BALB/c mice and they were treated with a subcutaneous injection every 3 days. Results Dose-dependent growth inhibition in vitro was observed with 50% inhibition occurring at 600 ng/ml. Angiogenesis assay revealed that administration of TNP-470 inhibited the angiogenesis induced by Renca in a dose-dependent manner. In the subcutaneous experiment, TNP-470 decreased the growth rate of established subcutaneous tumours rather than reduced the size of the tumour. The administration of TNP-470 in mice with lung metastasis inhibited the development of metastasis of Renca without weight loss or diarrhoea. Conclusion The present study demonstrated that TNP-470 had an inhibitory effect on tumour-induced angiogenesis and a significant anti-tumour effect on Renca. This suggests that TNP-470 could be useful in the treatment of renal cell carcinoma. Further studies are needed to clarify whether TNP-470 is more effective when combined with other drugs such as interferons.