TY - JOUR
T1 - Inhibition of in vivo proliferation of androgen-independent prostate cancers by an antagonist of growth hormone-releasing hormone
AU - Jungwirth, A.
AU - Schally, A. V.
AU - Pinski, J.
AU - Halmos, G.
AU - Groot, K.
AU - Armatis, P.
AU - Vadillo-Buenfil, M.
N1 - Funding Information:
The authors thank Ms Dora Rigo, Ms Elena Glotser and Mr Harold Valerio for technical assistance and Professor J Frick for his support. The gifts of materials used in RIA from the National Hormone and Pituitary Program (NHPP) of the National Institute of Diabetes and Digestive and Kidney Diseases (NATCH) and from Dr AF Parlow (Pituitary Hormones and Antisera Center, Torrance, CA, USA) are greatly appreciated. The work described in this paper was supported by the Medical Research Service of the Veterans Affairs Department (to AVS) and by a grant from Pierre Fabre Medicament to Tulane University School of Medicine and. AJ is a recipient of a fellowship from the Fond zur Forderung der wissenschaftlichen Forschung, Austria.
PY - 1997
Y1 - 1997
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.
AB - 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.
KW - DU-145
KW - Dunning tumour
KW - Growth hormone-releasing hormone antagonist
KW - Insulin-like growth factor
KW - PC-3
KW - Prostate cancer
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U2 - 10.1038/bjc.1997.271
DO - 10.1038/bjc.1997.271
M3 - Article
C2 - 9184172
AN - SCOPUS:0030979558
VL - 75
SP - 1585
EP - 1592
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 11
ER -
