Inhibition of in vivo proliferation of androgen-independent prostate cancers by an antagonist of growth hormone-releasing hormone.
Jungwirth. A A; Schally. A V AV; Pinski. J J; Halmos. G G; Groot. K K; Armatis. P P; Vadillo-Buenfil. M M
Key Findings
- Blocking GH‑RH with the antagonist MZ‑4‑71 reduced tumor size and slowed growth in two human prostate cancer cell lines grown in mice.
- Treated animals showed lower blood levels of growth hormone (GH) and IGF‑I, and the tumors themselves had almost no IGF‑I or IGF‑II.
- The effect was seen in both mouse and rat models, suggesting the mechanism works across species.
Practical Outcomes
- For DIY health enthusiasts, this research doesn’t provide a usable protocol because the drug tested isn’t available to the public and the work is limited to animal models. It does hint that lowering GH or IGF signaling might influence cancer growth, but any self‑experimentation would be speculative and potentially unsafe.
Summary
In mice and rats with aggressive prostate cancers, a drug that blocks the hormone that normally makes the body release growth hormone (called a GH‑RH antagonist) shrank the tumors and lowered levels of growth‑related proteins. The study was done only in animals and used a compound that isn’t sold as a supplement.
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 microg 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 and 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 microg of MZ-4-71 day(-1) 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-1 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.
Study Information
pubmed
1997
1997-06-01T00:00:00.000Z
10.1038/bjc.1997.271
87
40