Inhibition of in vivo proliferation of androgen-independent prostate cancers by an antagonist of growth hormone-releasing hormone

A. Jungwirth, Andrew V Schally, J. Pinski, G. Halmos, K. Groot, P. Armatis, M. Vadillo-Buenfil

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Tumour-inhibitory effects of a new antagonist of growth hormone-releasing hormone (GH-RH), MZ-4-71, were evaluated in nude mice bearing androgen-independent human prostate cancer cell lines DU-145 and PC-3 and in Copenhagen rats implanted with Dunning R-3327 AT-1 prostatic adenocarcinoma. After 6 weeks of therapy, the tumour volume in nude mice with DU-145 prostate cancers treated with 40 μg day-1 MZ-4-71 was significantly decreased to 37 ± 13 mm3 (P < 0.01) compared with controls that measured 194 ± 35 mm3. A similar inhibition of tumour growth was obtained in nude mice bearing PC-3 cancers, in which the treatment with MZ-4-71 for 4 weeks diminished the tumour volume to 119 ± 35 mm3 compared with 397 ± 115 mm3 for control animals. Therapy with MZ-4-71 also significantly decreased weights of PC-3 acid DU-145 tumours and increased tumour doubling time. Serum levels of GH and IGF-I were significantly decreased in animals treated with GH-RH antagonist..In PC-3 tumour tissue, the levels of IGF-I and IGF-II were reduced to non-detectable values after therapy with MZ-4-71. The growth of Dunning R-3327 AT-1 tumours in rats was also significantly inhibited after 3 weeks of treatment with 100 μg of MZ-4-71 day-l i.p. as shown by a reduction in tumour volume and weight (both P-values < 0.05). Specific high-affinity binding sites for IGF-I were found on the membranes of DU-145, PC-3 and Dunning R-3327 AT-1 tumours. Our results indicate that GH-RH antagonist MZ-4-71 suppresses growth of PC-3, DU-145 and Dunning AT-I androgen-independent prostate cancers, through diminution of GH release and the resulting decrease in the secretion of hepatic IGF-I, or through mechanisms involving a lowering of tumour IGF-I levels and possibly an inhibition of tumour IGF-I and IGF-II production. GH-RH antagonists could be considered for further development for the therapy of prostate cancer, especially after the relapse.

Original languageEnglish
Pages (from-to)1585-1592
Number of pages8
JournalBritish Journal of Cancer
Volume75
Issue number11
StatePublished - Jun 12 1997
Externally publishedYes

Fingerprint

Growth Hormone-Releasing Hormone
Androgens
Prostatic Neoplasms
Insulin-Like Growth Factor I
Neoplasms
Tumor Burden
Hormone Antagonists
Nude Mice
Insulin-Like Growth Factor II
Growth
Therapeutics
MZ 4-71
Adenocarcinoma
Binding Sites
Weights and Measures
Recurrence
Cell Line

Keywords

  • DU-145
  • Dunning tumour
  • Growth hormone-releasing hormone antagonist
  • Insulin-like growth factor
  • PC-3
  • Prostate cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Jungwirth, A., Schally, A. V., Pinski, J., Halmos, G., Groot, K., Armatis, P., & Vadillo-Buenfil, M. (1997). Inhibition of in vivo proliferation of androgen-independent prostate cancers by an antagonist of growth hormone-releasing hormone. British Journal of Cancer, 75(11), 1585-1592.

Inhibition of in vivo proliferation of androgen-independent prostate cancers by an antagonist of growth hormone-releasing hormone. / Jungwirth, A.; Schally, Andrew V; Pinski, J.; Halmos, G.; Groot, K.; Armatis, P.; Vadillo-Buenfil, M.

In: British Journal of Cancer, Vol. 75, No. 11, 12.06.1997, p. 1585-1592.

Research output: Contribution to journalArticle

Jungwirth, A, Schally, AV, Pinski, J, Halmos, G, Groot, K, Armatis, P & Vadillo-Buenfil, M 1997, 'Inhibition of in vivo proliferation of androgen-independent prostate cancers by an antagonist of growth hormone-releasing hormone', British Journal of Cancer, vol. 75, no. 11, pp. 1585-1592.
Jungwirth, A. ; Schally, Andrew V ; Pinski, J. ; Halmos, G. ; Groot, K. ; Armatis, P. ; Vadillo-Buenfil, M. / Inhibition of in vivo proliferation of androgen-independent prostate cancers by an antagonist of growth hormone-releasing hormone. In: British Journal of Cancer. 1997 ; Vol. 75, No. 11. pp. 1585-1592.
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abstract = "Tumour-inhibitory effects of a new antagonist of growth hormone-releasing hormone (GH-RH), MZ-4-71, were evaluated in nude mice bearing androgen-independent human prostate cancer cell lines DU-145 and PC-3 and in Copenhagen rats implanted with Dunning R-3327 AT-1 prostatic adenocarcinoma. After 6 weeks of therapy, the tumour volume in nude mice with DU-145 prostate cancers treated with 40 μg day-1 MZ-4-71 was significantly decreased to 37 ± 13 mm3 (P < 0.01) compared with controls that measured 194 ± 35 mm3. A similar inhibition of tumour growth was obtained in nude mice bearing PC-3 cancers, in which the treatment with MZ-4-71 for 4 weeks diminished the tumour volume to 119 ± 35 mm3 compared with 397 ± 115 mm3 for control animals. Therapy with MZ-4-71 also significantly decreased weights of PC-3 acid DU-145 tumours and increased tumour doubling time. Serum levels of GH and IGF-I were significantly decreased in animals treated with GH-RH antagonist..In PC-3 tumour tissue, the levels of IGF-I and IGF-II were reduced to non-detectable values after therapy with MZ-4-71. The growth of Dunning R-3327 AT-1 tumours in rats was also significantly inhibited after 3 weeks of treatment with 100 μg of MZ-4-71 day-l i.p. as shown by a reduction in tumour volume and weight (both P-values < 0.05). Specific high-affinity binding sites for IGF-I were found on the membranes of DU-145, PC-3 and Dunning R-3327 AT-1 tumours. Our results indicate that GH-RH antagonist MZ-4-71 suppresses growth of PC-3, DU-145 and Dunning AT-I androgen-independent prostate cancers, through diminution of GH release and the resulting decrease in the secretion of hepatic IGF-I, or through mechanisms involving a lowering of tumour IGF-I levels and possibly an inhibition of tumour IGF-I and IGF-II production. GH-RH antagonists could be considered for further development for the therapy of prostate cancer, especially after the relapse.",
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N2 - Tumour-inhibitory effects of a new antagonist of growth hormone-releasing hormone (GH-RH), MZ-4-71, were evaluated in nude mice bearing androgen-independent human prostate cancer cell lines DU-145 and PC-3 and in Copenhagen rats implanted with Dunning R-3327 AT-1 prostatic adenocarcinoma. After 6 weeks of therapy, the tumour volume in nude mice with DU-145 prostate cancers treated with 40 μg day-1 MZ-4-71 was significantly decreased to 37 ± 13 mm3 (P < 0.01) compared with controls that measured 194 ± 35 mm3. A similar inhibition of tumour growth was obtained in nude mice bearing PC-3 cancers, in which the treatment with MZ-4-71 for 4 weeks diminished the tumour volume to 119 ± 35 mm3 compared with 397 ± 115 mm3 for control animals. Therapy with MZ-4-71 also significantly decreased weights of PC-3 acid DU-145 tumours and increased tumour doubling time. Serum levels of GH and IGF-I were significantly decreased in animals treated with GH-RH antagonist..In PC-3 tumour tissue, the levels of IGF-I and IGF-II were reduced to non-detectable values after therapy with MZ-4-71. The growth of Dunning R-3327 AT-1 tumours in rats was also significantly inhibited after 3 weeks of treatment with 100 μg of MZ-4-71 day-l i.p. as shown by a reduction in tumour volume and weight (both P-values < 0.05). Specific high-affinity binding sites for IGF-I were found on the membranes of DU-145, PC-3 and Dunning R-3327 AT-1 tumours. Our results indicate that GH-RH antagonist MZ-4-71 suppresses growth of PC-3, DU-145 and Dunning AT-I androgen-independent prostate cancers, through diminution of GH release and the resulting decrease in the secretion of hepatic IGF-I, or through mechanisms involving a lowering of tumour IGF-I levels and possibly an inhibition of tumour IGF-I and IGF-II production. GH-RH antagonists could be considered for further development for the therapy of prostate cancer, especially after the relapse.

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