Direct effects of GnRH agonists in human hormone-sensitive endometrial cells

The antiproliferative: effect of two GnRH agonists (leuprorelin acetate and triptorelin), alone or combined with tamoxifen (TAM) or medroxyprogesteron e acetate (MPA), on human estrogen-sensitive endometrial cancer cells (Ishi kawa) was investigated. Although ineffective when tested alone in all the c ulture conditions used, both analogues counteracted or even suppressed the estrogen-stimulated growth of Ishikawa cells. The antiestrogenic effect of TAM or MPA was not modified by their association with high doses of the GnR H analogues, but low concentrations of triptorelin combined with MPA 10(-7) M determined a reduction in cell numbers which was greater than that obtai ned with the progestin or the analogue alone. In addition, analogue treatme nt prevented the estrogen-induced decrease in the level of estrogen recepto rs. Our data provide evidence that GnRH agonists can directly inhibit estro gen-stimulated endometrial cancer cell growth and suggest that they map int erfere with steroid-receptor machinery. (C) 2001 Elsevier Science Ireland L td. All rights reserved.