GROWTH-INHIBITORY EFFECTS OF LUTEINIZING-HORMONE-RELEASING HORMONE (LHRH) AGONISTS ON XENOGRAFTS OF THE DU-145 HUMAN ANDROGEN-INDEPENDENT PROSTATE-CANCER CELL-LINE IN NUDE-MICE

Experiments have been performed to clarify whether LHRH agonists might decrease growth of hormone-unresponsive prostate cancer in vivo. Male nude mice were injected s.c. with the human androgen-independent pros tate tumor DU 145 cells; osmotic minipumps releasing the LHRH agonist Zoladex (LHRH-A) for 14 days were simultaneously implanted under the s kin. Treatment with LHRH-A induced a significant decrease in tumor gro wth up to the end of the treatment. In subsequent experiment, minipump s releasing LHRH-A were implanted in nude mice either 7 or 14 days aft er cell inoculation. When the treatment was started 7 days after inocu lation of the cells, tumor growth was significantly decreased up to 28 days; thereafter, tumor volume remained lower than in controls, altho ugh not significantly. When LHRH-A was administered beginning 14 days after cell inoculation, tumor growth was not significantly affected at any time interval considered. LHRH-A did not appear to induce apoptos is in DU 145 cells, at least on the basis of the apoptotic index and i mmunohistochemical staining of the p53 protein. On the other hand, tre atment with LHRH-A was accompanied by a significant decrease of the co ncentration of epidermal growth factor receptors in DU 145 prostate ca ncer specimens. Our results show that the LHRH agonist used significan tly inhibits the growth of DU 145 androgen-independent prostate tumor xenografts in nude mice. (C) 1996 Wiley-Liss, Inc.