Potentiation of the inhibitory effect of growth hormone-releasing hormone antagonists on PC-3 human prostate cancer by bombesin antagonists indicative of interference with both IGF and EGF pathways

Artur Plonowski, Andrew V Schally, Jozsef L. Varga, Zoltan Rekasi, Francine Hebert, Gabor Halmos, Kate Groot

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

BACKGROUND. In view of the involvement of various neuropeptides and growth factors in the progression of androgen-independent prostate cancer, we investigated the effects of antagonists of growth hormone-releasing hormone (GHRH) alone or in combination with an antagonist of bombesin/gastrin- releasing peptide (BN/GRP) on PC-3 human prostate cancers. METHODS. Nude mice implanted with PC-3 tumors received GHRH antagonists MZ-5-156 or JV-1-38, each at 20 μg/day s.c. In experiment 2, treatment consisted of daily injections of JV-1-38 (20 μg), BN/GRP antagonist RC-3940-II (10 μg), or a combination of JV-1-38 and RC-3940-II. Serum IGF-I levels, expression of mRNA for IGF-II, and characteristics of BN/GRP and EGF receptors in tumor tissue were investigated. RESULTS. JV-1-38 induced a greater inhibition of tumor growth and suppression of IGF-II mRNA than MZ-5-156, both compounds causing a similar decrease in serum IGF-I. In experiment 2, JV-1-38 and RC-3940-II produced a comparable reduction in tumor volume (65% and 61%, respectively), but a combination of both antagonists augmented tumor inhibition to 75%. Combined treatment with JV-1-38 and RC-3940-II also led to a greater suppression of IGF-II mRNA (92%), as compared with JV-1-38 (72%) or RC-3940- II (77%). Serum IGF-I concentration was lowered only in mice treated with JV- 1-38, while the downregulation of BN/GRP and EGF receptors was specific for groups receiving RC-3940-II. CONCLUSIONS. The inhibitory effects of GHRH antagonists on PC-3 human androgen-independent prostate cancer can be potentiated by concomitant use of BN/GRP antagonists. The combination of both types of analogs apparently interferes with both IGF and bombesin/EGF pathways, and might be clinically useful for the management of androgen- independent prostate cancer. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)172-180
Number of pages9
JournalProstate
Volume44
Issue number2
DOIs
StatePublished - Jul 1 2000
Externally publishedYes

Fingerprint

Hormone Antagonists
Bombesin
Growth Hormone-Releasing Hormone
Epidermal Growth Factor
Gastrin-Releasing Peptide
Prostatic Neoplasms
Insulin-Like Growth Factor II
Insulin-Like Growth Factor I
Androgens
Messenger RNA
Neoplasms
Serum
JV 1-38
Tumor Burden
Neuropeptides
Nude Mice
Hca(6)-Leu(13)-psi(CH2N)-Tac(14)-bombesin(6-14)
Intercellular Signaling Peptides and Proteins
Down-Regulation
Injections

Keywords

  • Androgen-independent prostate cancer
  • Antagonist of bombesin/gastrin-releasing peptide
  • Antagonist of growth hormone- releasing hormone
  • Epidermal growth factor
  • Insulin-like growth factor

ASJC Scopus subject areas

  • Urology

Cite this

Potentiation of the inhibitory effect of growth hormone-releasing hormone antagonists on PC-3 human prostate cancer by bombesin antagonists indicative of interference with both IGF and EGF pathways. / Plonowski, Artur; Schally, Andrew V; Varga, Jozsef L.; Rekasi, Zoltan; Hebert, Francine; Halmos, Gabor; Groot, Kate.

In: Prostate, Vol. 44, No. 2, 01.07.2000, p. 172-180.

Research output: Contribution to journalArticle

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title = "Potentiation of the inhibitory effect of growth hormone-releasing hormone antagonists on PC-3 human prostate cancer by bombesin antagonists indicative of interference with both IGF and EGF pathways",
abstract = "BACKGROUND. In view of the involvement of various neuropeptides and growth factors in the progression of androgen-independent prostate cancer, we investigated the effects of antagonists of growth hormone-releasing hormone (GHRH) alone or in combination with an antagonist of bombesin/gastrin- releasing peptide (BN/GRP) on PC-3 human prostate cancers. METHODS. Nude mice implanted with PC-3 tumors received GHRH antagonists MZ-5-156 or JV-1-38, each at 20 μg/day s.c. In experiment 2, treatment consisted of daily injections of JV-1-38 (20 μg), BN/GRP antagonist RC-3940-II (10 μg), or a combination of JV-1-38 and RC-3940-II. Serum IGF-I levels, expression of mRNA for IGF-II, and characteristics of BN/GRP and EGF receptors in tumor tissue were investigated. RESULTS. JV-1-38 induced a greater inhibition of tumor growth and suppression of IGF-II mRNA than MZ-5-156, both compounds causing a similar decrease in serum IGF-I. In experiment 2, JV-1-38 and RC-3940-II produced a comparable reduction in tumor volume (65{\%} and 61{\%}, respectively), but a combination of both antagonists augmented tumor inhibition to 75{\%}. Combined treatment with JV-1-38 and RC-3940-II also led to a greater suppression of IGF-II mRNA (92{\%}), as compared with JV-1-38 (72{\%}) or RC-3940- II (77{\%}). Serum IGF-I concentration was lowered only in mice treated with JV- 1-38, while the downregulation of BN/GRP and EGF receptors was specific for groups receiving RC-3940-II. CONCLUSIONS. The inhibitory effects of GHRH antagonists on PC-3 human androgen-independent prostate cancer can be potentiated by concomitant use of BN/GRP antagonists. The combination of both types of analogs apparently interferes with both IGF and bombesin/EGF pathways, and might be clinically useful for the management of androgen- independent prostate cancer. (C) 2000 Wiley-Liss, Inc.",
keywords = "Androgen-independent prostate cancer, Antagonist of bombesin/gastrin-releasing peptide, Antagonist of growth hormone- releasing hormone, Epidermal growth factor, Insulin-like growth factor",
author = "Artur Plonowski and Schally, {Andrew V} and Varga, {Jozsef L.} and Zoltan Rekasi and Francine Hebert and Gabor Halmos and Kate Groot",
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T1 - Potentiation of the inhibitory effect of growth hormone-releasing hormone antagonists on PC-3 human prostate cancer by bombesin antagonists indicative of interference with both IGF and EGF pathways

AU - Plonowski, Artur

AU - Schally, Andrew V

AU - Varga, Jozsef L.

AU - Rekasi, Zoltan

AU - Hebert, Francine

AU - Halmos, Gabor

AU - Groot, Kate

PY - 2000/7/1

Y1 - 2000/7/1

N2 - BACKGROUND. In view of the involvement of various neuropeptides and growth factors in the progression of androgen-independent prostate cancer, we investigated the effects of antagonists of growth hormone-releasing hormone (GHRH) alone or in combination with an antagonist of bombesin/gastrin- releasing peptide (BN/GRP) on PC-3 human prostate cancers. METHODS. Nude mice implanted with PC-3 tumors received GHRH antagonists MZ-5-156 or JV-1-38, each at 20 μg/day s.c. In experiment 2, treatment consisted of daily injections of JV-1-38 (20 μg), BN/GRP antagonist RC-3940-II (10 μg), or a combination of JV-1-38 and RC-3940-II. Serum IGF-I levels, expression of mRNA for IGF-II, and characteristics of BN/GRP and EGF receptors in tumor tissue were investigated. RESULTS. JV-1-38 induced a greater inhibition of tumor growth and suppression of IGF-II mRNA than MZ-5-156, both compounds causing a similar decrease in serum IGF-I. In experiment 2, JV-1-38 and RC-3940-II produced a comparable reduction in tumor volume (65% and 61%, respectively), but a combination of both antagonists augmented tumor inhibition to 75%. Combined treatment with JV-1-38 and RC-3940-II also led to a greater suppression of IGF-II mRNA (92%), as compared with JV-1-38 (72%) or RC-3940- II (77%). Serum IGF-I concentration was lowered only in mice treated with JV- 1-38, while the downregulation of BN/GRP and EGF receptors was specific for groups receiving RC-3940-II. CONCLUSIONS. The inhibitory effects of GHRH antagonists on PC-3 human androgen-independent prostate cancer can be potentiated by concomitant use of BN/GRP antagonists. The combination of both types of analogs apparently interferes with both IGF and bombesin/EGF pathways, and might be clinically useful for the management of androgen- independent prostate cancer. (C) 2000 Wiley-Liss, Inc.

AB - BACKGROUND. In view of the involvement of various neuropeptides and growth factors in the progression of androgen-independent prostate cancer, we investigated the effects of antagonists of growth hormone-releasing hormone (GHRH) alone or in combination with an antagonist of bombesin/gastrin- releasing peptide (BN/GRP) on PC-3 human prostate cancers. METHODS. Nude mice implanted with PC-3 tumors received GHRH antagonists MZ-5-156 or JV-1-38, each at 20 μg/day s.c. In experiment 2, treatment consisted of daily injections of JV-1-38 (20 μg), BN/GRP antagonist RC-3940-II (10 μg), or a combination of JV-1-38 and RC-3940-II. Serum IGF-I levels, expression of mRNA for IGF-II, and characteristics of BN/GRP and EGF receptors in tumor tissue were investigated. RESULTS. JV-1-38 induced a greater inhibition of tumor growth and suppression of IGF-II mRNA than MZ-5-156, both compounds causing a similar decrease in serum IGF-I. In experiment 2, JV-1-38 and RC-3940-II produced a comparable reduction in tumor volume (65% and 61%, respectively), but a combination of both antagonists augmented tumor inhibition to 75%. Combined treatment with JV-1-38 and RC-3940-II also led to a greater suppression of IGF-II mRNA (92%), as compared with JV-1-38 (72%) or RC-3940- II (77%). Serum IGF-I concentration was lowered only in mice treated with JV- 1-38, while the downregulation of BN/GRP and EGF receptors was specific for groups receiving RC-3940-II. CONCLUSIONS. The inhibitory effects of GHRH antagonists on PC-3 human androgen-independent prostate cancer can be potentiated by concomitant use of BN/GRP antagonists. The combination of both types of analogs apparently interferes with both IGF and bombesin/EGF pathways, and might be clinically useful for the management of androgen- independent prostate cancer. (C) 2000 Wiley-Liss, Inc.

KW - Androgen-independent prostate cancer

KW - Antagonist of bombesin/gastrin-releasing peptide

KW - Antagonist of growth hormone- releasing hormone

KW - Epidermal growth factor

KW - Insulin-like growth factor

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