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Luteinizing hormone‐releasing hormone antagonist Cetrorelix (SB‐75) and bombesin antagonist RC‐3940‐II inhibit the growth of androgen‐independent PC‐3 prostate cancer in nude mice
Author(s) -
Jungwirth Andreas,
Galvan Georg,
Pinski Jacek,
Halmos Gabor,
Szepeshazi Karoly,
Cai RenZhi,
Groot Kate,
Schally Andrew V.
Publication year - 1997
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(19970801)32:3<164::aid-pros2>3.0.co;2-l
Subject(s) - antagonist , prostate cancer , endocrinology , hormone antagonist , medicine , luteinizing hormone , androgen , testosterone (patch) , bombesin , gonadotropin releasing hormone antagonist , hormone , cancer , gonadotropin releasing hormone , receptor , neuropeptide
BACKGROUND Hormones like bombesin (BN)/gastrin‐releasing peptide (GRP) and luteinizing hormone‐releasing hormone (LH‐RH) and growth factors such as epidermal growth factor (EGF) might be involved in the relapse of prostate cancer under androgen ablation therapy. Interference with receptors for BN/GRP, LH‐RH, or EGF might provide a therapeutic approach to inhibit tumor growth of androgen‐independent prostate cancer. METHODS LH‐RH antagonist Cetrorelix (SB‐75) and the BN/GRP antagonist RC‐3940‐II were tested for their effects on the growth of the androgen‐independent PC‐3 human prostate cancer cell line xenografted into nude mice. Tumor growth, serum hormone levels, and receptor concentrations for BN/GRP and EGF were measured. RESULTS When the treatment was started, tumor volume in all groups was 70–80 mm 3 . After 4 weeks, tumor volume in the control animals injected with saline was 871 ± 233 mm 3 and that of animals treated with Cetrorelix only 197 ± 61 mm 3 . The BN/GRP antagonist RC‐3940‐II also significantly reduced PC‐3 tumor volume in nude mice to 122 ± 20 mm 3 . The combination of Cetrorelix and RC‐3940‐II produced no additional inhibition. High‐affinity receptors for EGF were detected in the tumor membranes and their number was significantly decreased after administration of Cetrorelix or RC‐3940‐II. CONCLUSIONS These findings demonstrate that LH‐RH antagonists and BN/GRP antagonists inhibit the growth of the androgen‐independent prostate cancer cell line PC‐3 in vivo. Both analogs may exert a direct inhibitory effect on tumor growth through a down‐regulation of EGF receptors. Prostate 32:164–172, 1997. © 1997 Wiley‐Liss, Inc.