The combination of antagonists of LHRH with antagonists of GHRH improves inhibition of androgen sensitive MDA-PCa-2b and LuCaP-35 prostate cancers

Anton Stangelberger, Andrew V Schally, Marta Zarandi, Elmar Heinrich, Kate Groot, Alexandre Havt, Celia A. Kanashiro, Jozsef L. Varga, Gabor Halmos

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 languageEnglish
Pages (from-to)1339-1353
Number of pages15
JournalProstate
Volume67
Issue number12
DOIs
StatePublished - Sep 1 2007

Fingerprint

Hormone Antagonists
Growth Hormone-Releasing Hormone
Gonadotropin-Releasing Hormone
Androgens
Prostatic Neoplasms
Castration
LHRH Receptors
Passive Cutaneous Anaphylaxis
Epidermal Growth Factor
Heterografts
Nude Mice
Vascular Endothelial Growth Factor A
MZ-J-7-118
Neoplasms
Recurrence

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 journalArticle

Stangelberger, A, Schally, AV, Zarandi, M, Heinrich, E, Groot, K, Havt, A, Kanashiro, CA, Varga, JL & Halmos, G 2007, 'The combination of antagonists of LHRH with antagonists of GHRH improves inhibition of androgen sensitive MDA-PCa-2b and LuCaP-35 prostate cancers', Prostate, vol. 67, no. 12, pp. 1339-1353. https://doi.org/10.1002/pros.20605
Stangelberger, Anton ; Schally, Andrew V ; Zarandi, Marta ; Heinrich, Elmar ; Groot, Kate ; Havt, Alexandre ; Kanashiro, Celia A. ; Varga, Jozsef L. ; Halmos, Gabor. / The combination of antagonists of LHRH with antagonists of GHRH improves inhibition of androgen sensitive MDA-PCa-2b and LuCaP-35 prostate cancers. In: Prostate. 2007 ; Vol. 67, No. 12. pp. 1339-1353.
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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.",
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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.

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KW - LHRH antagonists

KW - Prostate cancer

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