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 angiogenesis assay and cell counting with dye exclusion. In the angiogenesis assay, Renca cells were injected intradermally 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.
OBJECTIVE: To evaluate the antitumour effect of an angio-inhibitory drug, a synthetic analogue of fumagillin (TNP-470), on murinerenal 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 angiogenesis assay and cell counting with dye exclusion. In the angiogenesis assay, Renca cells were injected intradermally 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.
Authors: Maria A Rupnick; Dipak Panigrahy; Chen-Yu Zhang; Susan M Dallabrida; Bradford B Lowell; Robert Langer; M Judah Folkman Journal: Proc Natl Acad Sci U S A Date: 2002-07-29 Impact factor: 11.205