Abstract
BACKGROUND. Antagonists of growth hormone-releasing hormone (GHRH) could extend the duration of response of androgen sensitive prostate cancers to androgen deprivation. METHODS. We investigated the effect of new GHRH antagonists MZ-J-7-118 and MZ-J-7-138 and luteinizing hormone-releasing hormone (LHRH) antagonist Cetrorelix or castration on androgen sensitive MDA-PCa-2b and LuCaP-35 prostate cancer models xenografted into nude mice. Animals bearing androgen-independent LuCaP-35V prostatic cancer model were also treated with MZ-J-7-118. RESULTS. Receptors for LHRH and GHRH were present in MDA-PCA-2b, LuCaP-35, and LuCaP-35V tumors. GHRH antagonists increased the inhibitory effect of surgical castration and LHRH antagonists on androgen sensitive MDA-PCa-2b and LuCaP-35 rumors. The time to relapse of androgen-dependent LuCaP-35 tumors was extended by GHRH antagonists. Growth of androgen-independent LuCaP-35V xenografts was also significantly inhibited by MZ-J-7-118. In MDA-PCa-2b rumors treatment with MZ-J-7-118 caused a significant decrease of VEGF and Cetrorelix or its combination with MZ-J-7-118 reduced EGF. The Bmax of EGF receptors was significantly reduced by Cetrorelix, MZ-J-7-118 and their combination. CONCLUSIONS. Our findings suggest that the use of a combination of antagonists of GHRH and LHRH could improve the therapy for androgen sensitive prostate cancer. Antagonists of GHRH could be also considered for treatment of androgen-independent prostate cancers.
Original language | English (US) |
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Pages (from-to) | 1339-1353 |
Number of pages | 15 |
Journal | Prostate |
Volume | 67 |
Issue number | 12 |
DOIs | |
State | Published - Sep 1 2007 |
Keywords
- GHRH antagonists
- LHRH antagonists
- Prostate cancer
ASJC Scopus subject areas
- Urology