Plausible novel therapeutic strategy of uterine endometrial cancer with reduction of basic fibroblast growth factor secretion by progestin and O-(chloroacetyl-carbamoyl) fumagillol (TNP-470; AGM-1470)

To know the potential of growth, invasion and metastasis of endometrial cancer associated with neovascularization, the effects of sex steroids and O-(chloroacetyl-carbamoyl) fumagillol (TNP-470; AGM-1470) on basic fibroblast growth factor (FGF) expression and secretion and its mRNA expression were investigated in well-differentiated endometrial cancer cell line Ishikawa and in undifferentiated endometrial cancer cell line AN3 CA. Basic FGF expression and secretion and its mRNA expression in Ishikawa cells, but not in AN3 CA cells, were increased by estrogen, while progesterone diminished the estrogen-induced increases. TNP-470 reduced the levels regardless of estrogen treatment in AN3 CA cells. Therefore, basic FGF secretion may be inhibited by progestin in differentiated cells, and by TNP-470 in undifferentiated cells. Since endometrial cancer consists of differentiated and undifferentiated cells as heterogeneity, a combination therapy for endometrial cancer with progestin and TNP470 might be effective.