Effect of angiogenesis inhibitor TNP-470 on vascular formation in pituitary tumors induced by estrogen in rats.

TNP-470 (TNP), an analog of fumagillin, inhibits cell proliferation and tumorigenesis in estrogen-induced pituitary tumors in rats. This study found that treatment with TNP or TNP and bromocriptine suppressed vascular formation in these pituitary tumors more than bromocriptine alone. TNP had a greater suppressive effect on vascular formation in pituitary tumors than in normal pituitary gland. Laminin and basic fibroblast growth factor (FGF) were detected around new blood vessels in normal pituitary gland and pituitary tumor. TNP did not completely suppress laminin or basic FGF expression. The effect of TNP on pituitary tumor may involve inhibition of vascular formation by mechanisms mediated by other factors in addition to basic FGF. Treatment with bromocriptine and TNP acts indirectly and directly on vascular formation and may provide a useful chemotherapeutic modality for pituitary tumors.