help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chatzistamou, I.
Right arrow Articles by Halmos, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chatzistamou, I.
Right arrow Articles by Halmos, G.
The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 5 2144-2152
Copyright © 2001 by The Endocrine Society

Original Studies

Antagonists of Growth Hormone-Releasing Hormone and Somatostatin Analog RC-160 Inhibit the Growth of the OV-1063 Human Epithelial Ovarian Cancer Cell Line Xenografted into Nude Mice1

Ioulia Chatzistamou, Andrew V. Schally, Jozsef L. Varga, Kate Groot, Patricia Armatis, Rebeca Busto and Gabor Halmos

Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center (I.C., A.V.S., J.L.V., K.G., P.A., R.B., G.H.), and Section of Experimental Medicine, Department of Medicine, Tulane University School of Medicine (I.C., A.V.S., J.L.V., R.B., G.H.), New Orleans, Louisiana 70112

Address all correspondence and requests for reprints to: Dr. Andrew V. Schally, Endocrine, Polypeptide, and Cancer Institute, Veteran Affairs Medical Center, 1601 Perdido Street, New Orleans, Louisiana 70112-1262.

The effects of antagonists of GHRH and the somatostatin analog RC-160 on the growth of OV-1063 human epithelial ovarian cancer cells xenografted into nude mice were investigated. Treatment with 20 µg/day of the GHRH antagonist JV-1-36 or MZ-5-156 and 60 µg/day of the somatostatin analog RC-160 for 25 days decreased tumor volume by 70.9% (P < 0.01), 58.3% (P < 0.05), and 60.6% (P < 0.01), respectively, vs. the control value. The levels of GH in serum were decreased in all of the treated groups, but only RC-160 significantly reduced serum insulin-like growth factor I (IGF-I). The levels of messenger ribonucleic acid (mRNA) for IGF-I and -II and for their receptors in OV-1063 tumors were investigated by multiplex RT-PCR. No expression of mRNA for IGF-I was detected, but treatment with JV-1-136 caused a 51.8% decrease (P < 0.05) in the level of mRNA for IGF-II in tumors. Exposure of OV-1063 cells cultured in vitro to GHRH, IGF-I, or IGF-II significantly (P < 0.05) stimulated cell growth, but 10-5 mol/L JV-1-36 nearly completely inhibited (P < 0.001) OV-1063 cell proliferation. OV-1063 tumors expressed mRNA for GHRH receptors and showed the presence of binding sites for GHRH. Our results indicate that antagonistic analogs of GHRH and the somatostatin analog RC-160 inhibit the growth of epithelial ovarian cancers. The effects of RC-160 seem to be exerted more on the pituitary GH-hepatic IGF-I axis, whereas GHRH antagonists appear to reduce IGF-II production and interfere with the autocrine regulatory pathway. The antitumorigenic action of GHRH antagonists appears to be mediated by GHRH receptors found in OV-1063 tumors.




This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Buchholz, A. V. Schally, J. B. Engel, F. Hohla, E. Heinrich, F. Koester, J. L. Varga, and G. Halmos
Potentiation of mammary cancer inhibition by combination of antagonists of growth hormone-releasing hormone with docetaxel
PNAS, February 6, 2007; 104(6): 1943 - 1946.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Havt, A. V. Schally, G. Halmos, J. L. Varga, G. L. Toller, J. E. Horvath, K. Szepeshazi, F. Koster, K. Kovitz, K. Groot, et al.
The expression of the pituitary growth hormone-releasing hormone receptor and its splice variants in normal and neoplastic human tissues
PNAS, November 29, 2005; 102(48): 17424 - 17429.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. B. Jaeger, W. A. Banks, J. L. Varga, and A. V. Schally
Antagonists of growth hormone-releasing hormone cross the blood-brain barrier: A potential applicability to treatment of brain tumors
PNAS, August 30, 2005; 102(35): 12495 - 12500.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
G. Keller, A. V. Schally, K. Groot, G. L. Toller, A. Havt, F. Koster, P. Armatis, G. Halmos, M. Zarandi, J. L. Varga, et al.
Effective treatment of experimental human non-Hodgkin's lymphomas with antagonists of growth hormone-releasing hormone
PNAS, July 26, 2005; 102(30): 10628 - 10633.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. B. Engel, G. Keller, A. V. Schally, G. L. Toller, K. Groot, A. Havt, P. Armatis, M. Zarandi, J. L. Varga, and G. Halmos
Inhibition of Growth of Experimental Human Endometrial Cancer by an Antagonist of Growth Hormone-Releasing Hormone
J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3614 - 3621.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Z. Rekasi, T. Czompoly, A. V. Schally, F. Boldizsar, J. L. Varga, M. Zarandi, T. Berki, R. A. Horvath, and P. Nemeth
Antagonist of growth hormone-releasing hormone induces apoptosis in LNCaP human prostate cancer cells through a Ca2+-dependent pathway
PNAS, March 1, 2005; 102(9): 3435 - 3440.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Z. Szereday, A. V. Schally, J. L. Varga, C. A. Kanashiro, F. Hebert, P. Armatis, K. Groot, K. Szepeshazi, G. Halmos, and R. Busto
Antagonists of Growth Hormone-Releasing Hormone Inhibit the Proliferation of Experimental Non-Small Cell Lung Carcinoma
Cancer Res., November 15, 2003; 63(22): 7913 - 7919.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. Kiaris, I. Chatzistamou, A. V. Schally, G. Halmos, J. L. Varga, H. Koutselini, and A. Kalofoutis
Ligand-dependent and -independent effects of splice variant 1 of growth hormone-releasing hormone receptor
PNAS, August 5, 2003; 100(16): 9512 - 9517.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
G. Halmos, A. V. Schally, T. Czompoly, M. Krupa, J. L. Varga, and Z. Rekasi
Expression of Growth Hormone-Releasing Hormone and Its Receptor Splice Variants in Human Prostate Cancer
J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4707 - 4714.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. Busto, A. V. Schally, J. L. Varga, M. O. Garcia-Fernandez, K. Groot, P. Armatis, and K. Szepeshazi
The expression of growth hormone-releasing hormone (GHRH) and splice variants of its receptor in human gastroenteropancreatic carcinomas
PNAS, September 3, 2002; 99(18): 11866 - 11871.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. Kiaris, A. V. Schally, R. Busto, G. Halmos, S. Artavanis-Tsakonas, and J. L. Varga
Expression of a splice variant of the receptor for GHRH in 3T3 fibroblasts activates cell proliferation responses to GHRH analogs
PNAS, January 1, 2002; (2002) 12590999.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. Kiaris, A. V. Schally, R. Busto, G. Halmos, S. Artavanis-Tsakonas, and J. L. Varga
Expression of a splice variant of the receptor for GHRH in 3T3 fibroblasts activates cell proliferation responses to GHRH analogs
PNAS, January 8, 2002; 99(1): 196 - 200.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2001 by The Endocrine Society