GROWTH-INHIBITION OF HUMAN PROSTATE TUMOR-CELLS BY AN AGONIST OF GONADOTROPIN-RELEASING-HORMONE

The effect of [D-Leu(6),des-Gly-NH210,Proethylamide(9)]-GnRH leuprolid e, was determined for the human primary prostate tumor cell line ALVA- 31 by in vitro mitogenic assays. Prostate tumor cell proliferation was inhibited up to 50% by leuprolide. Inhibition was not observed in par allel cultures treated with other low molecular weight bioactive pepti des. The incorporation and metabolic reduction of testosterone was not affected by concentrations of leuprolide that were inhibitory in the mitogenic assay. Specific high-affinity binding of I-125-labeled leupr olide was also demonstrated on intact tumor cells with an estimated ef fective median dose (ED(50)) of <1 x 10(-9)M. Inhibition of prostate t umor growth was further demonstrated in Balb/c athymic intact and cast rate male mice bearing ALVA-31 tumor xenografts following chronic admi nistration of leuprolide. These data clearly demonstrate that leuproli de can inhibit the growth of a human prostate carcinoma cell line. Stu dies conducted in castrate animals further suggest an alternative mech anism of growth inhibition that appears to be independent of the suppr ession of steroid hormone biosynthesis by LHRH analogues. (C) 1995 Wil ey-Liss, Inc.