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A correlation of endocrine and anticancer effects of some antagonists of GHRH.

Authors :
Kovács M
Schally AV
Hohla F
Rick FG
Pozsgai E
Szalontay L
Varga JL
Zarándi M
Source :
Peptides [Peptides] 2010 Oct; Vol. 31 (10), pp. 1839-46. Date of Electronic Publication: 2010 Jul 13.
Publication Year :
2010

Abstract

GHRH receptor antagonists inhibit growth and metastasis of a large number of experimental tumors expressing the pituitary GHRH receptor (pGHRH-R) and its major splice variant SV1. In this study, using Western blot, we demonstrated that DBTRG-05 and U-87MG human glioblastoma cell lines express pGHRH-R at levels 6-15 times higher than SV1. To reveal a correlation between the anticancer activity and the endocrine potency on inhibition of GH release, we compared the antitumor effect of GHRH antagonists JV-1-63 and MZJ-7-138 on growth of DBTRG-05 human glioblastomas grafted into athymic nude mice with their inhibitory potency on GH release. JV-1-63 strongly suppressed the stimulated GH secretion induced by clonidine in rats and inhibited the exogenous GHRH-induced GH surge by 88-99% in vivo and in vitro. MZJ-7-138 decreased the stimulated GH secretion by 58% in vitro and showed only a tendency to inhibit GH secretion in vivo. The strong inhibitor of GH release JV-1-63 reduced tumor growth of DBTRG-05 glioblastomas in nude mice by 46%, while the weak GH release suppressor MZJ-7-138 did not have an effect. Exposure of DBTRG-05 cells to the GHRH antagonists in vitro caused an upregulation of mRNA expression for pGHRH-R and a downregulation of SV1 expression, with JV-1-63 having significantly greater effects than MZJ-7-138. Our results demonstrate that a positive correlation exists between the endocrine potency and the antiproliferative efficacy of GHRH antagonists in tumors strongly expressing pGHRH-R.<br /> (Copyright © 2010 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1873-5169
Volume :
31
Issue :
10
Database :
MEDLINE
Journal :
Peptides
Publication Type :
Academic Journal
Accession number :
20633588
Full Text :
https://doi.org/10.1016/j.peptides.2010.07.006