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 rumors. 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 rumors 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 Bmax 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1339-1353 |
| Number of pages | 15 |
| Journal | Prostate |
| Volume | 67 |
| Issue number | 12 |
| DOIs | |
| State | Published - Sep 1 2007 |
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Keywords
- GHRH antagonists
- LHRH antagonists
- Prostate cancer
ASJC Scopus subject areas
- Urology
Cite this
The combination of antagonists of LHRH with antagonists of GHRH improves inhibition of androgen sensitive MDA-PCa-2b and LuCaP-35 prostate cancers. / Stangelberger, Anton; Schally, Andrew V; Zarandi, Marta; Heinrich, Elmar; Groot, Kate; Havt, Alexandre; Kanashiro, Celia A.; Varga, Jozsef L.; Halmos, Gabor.
In: Prostate, Vol. 67, No. 12, 01.09.2007, p. 1339-1353.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The combination of antagonists of LHRH with antagonists of GHRH improves inhibition of androgen sensitive MDA-PCa-2b and LuCaP-35 prostate cancers
AU - Stangelberger, Anton
AU - Schally, Andrew V
AU - Zarandi, Marta
AU - Heinrich, Elmar
AU - Groot, Kate
AU - Havt, Alexandre
AU - Kanashiro, Celia A.
AU - Varga, Jozsef L.
AU - Halmos, Gabor
PY - 2007/9/1
Y1 - 2007/9/1
N2 - 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 rumors. 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 rumors 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 Bmax 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.
AB - 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 rumors. 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 rumors 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 Bmax 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.
KW - GHRH antagonists
KW - LHRH antagonists
KW - Prostate cancer
UR - http://www.scopus.com/inward/record.url?scp=34548724461&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548724461&partnerID=8YFLogxK
U2 - 10.1002/pros.20605
DO - 10.1002/pros.20605
M3 - Article
VL - 67
SP - 1339
EP - 1353
JO - Prostate
JF - Prostate
SN - 0270-4137
IS - 12
ER -