ANGIOGENESIS INHIBITOR TNP-470 INHIBITS GROWTH AND METASTASIS OF A HORMONE-INDEPENDENT RAT PROSTATIC CARCINOMA CELL LINE

Purpose

Inhibitory effects of TNP-470, a synthetic analogue of the antibiotic fumagillin secreted by Aspergillus fumigatus, were studied with respect to growth and lung metastasis of the hormone-independent rat prostatic carcinoma cell line AT6.3.

Materials and Methods

Rat prostatic carcinoma AT6.3 cells were implanted in nude mice subcutaneously. Antimetastatic and growth-inhibitory effects of TNF-470 in vivo were examined 3 weeks after inoculation of AT6.3 cells. Direct growth-inhibitory effect was examined by MTT assay in vitro.

Results

TNP-470 inhibited the growth of AT6.3 cells in vitro. Subcutaneously injected TNP-470 markedly reduced numbers and individual size of lung metastases from AT6.3 cells inoculated percutaneously or intravenously into male BALB/c-nu/nu mice.

Conclusion

This agent, which acts as an angiogenesis inhibitor, may prove to be clinically useful in preventing metastasis of hormone-independent prostatic cancer.