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 language | English |
|---|---|
| Pages (from-to) | 172-180 |
| Number of pages | 9 |
| Journal | Prostate |
| Volume | 44 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jul 1 2000 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
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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UR - http://www.scopus.com/inward/citedby.url?scp=0034234650&partnerID=8YFLogxK
U2 - 10.1002/1097-0045(20000701)44:2<172::AID-PROS10>3.0.CO;2-Z
DO - 10.1002/1097-0045(20000701)44:2<172::AID-PROS10>3.0.CO;2-Z
M3 - Article
C2 - 10881027
AN - SCOPUS:0034234650
VL - 44
SP - 172
EP - 180
JO - Prostate
JF - Prostate
SN - 0270-4137
IS - 2
ER -