The combination of antagonists of LHRH with antagonists of GHRH improves inhibition of androgen sensitive MDA-PCa-2b and LuCaP-35 prostate cancers.

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 tumors. 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 tumors 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 B(max) 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.

• Authors: Anton Stangelberger, Andrew V Schally, Marta Zarandi, Elmar Heinrich, Kate Groot, Alexandre Havt, Celia A Kanashiro, Jozsef L Varga, Gabor Halmos
• Journal: The Prostate (Prostate) Vol. 67 Issue 12 Pg. 1339-53 (Sep 01 2007) ISSN: 0270-4137 [Print] United States
• PMID: 17624923 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hormone Antagonists
• MZ-J-7-118
• Vascular Endothelial Growth Factor A
• Gonadotropin-Releasing Hormone
• Epidermal Growth Factor
• Insulin-Like Growth Factor I
• Sermorelin
• Growth Hormone-Releasing Hormone
• Prostate-Specific Antigen
• cetrorelix

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Cell Line, Tumor
• Drug Synergism
• Epidermal Growth Factor (metabolism)
• Gonadotropin-Releasing Hormone (administration & dosage, analogs & derivatives, antagonists & inhibitors, pharmacology)
• Growth Hormone-Releasing Hormone (antagonists & inhibitors)
• Hormone Antagonists (administration & dosage, pharmacology)
• Humans
• Insulin-Like Growth Factor I (metabolism)
• Male
• Mice
• Mice, Nude
• Neoplasms, Hormone-Dependent (blood, drug therapy)
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms (blood, drug therapy)
• Sermorelin (administration & dosage, pharmacology)
• Vascular Endothelial Growth Factor A (metabolism)
• Xenograft Model Antitumor Assays