Growth hormone-releasing hormone antagonist MZ-4-71 inhibits in vivo proliferation of Caki-I renal adenocarcinoma.
Jungwirth. A A; Schally. A V AV; Pinski. J J; Groot. K K; Armatis. P P; Halmos. G G
Key Findings
- MZ‑4‑71 cut tumor size by about 90% in mice with renal cancer
- Treatment lowered serum GH, IGF‑I, liver IGF‑I, and tumor IGF‑I/II concentrations
- High doses of MZ‑4‑71 could inhibit cancer cell growth in a dish, but lower doses were ineffective
Practical Outcomes
- The main practical insight is that reducing the GH/IGF pathway may help slow certain cancers, but the specific antagonist used isn’t accessible for self‑experimentation. Using sermorelin, which raises GH, would likely have the opposite effect, so this study doesn’t provide a usable protocol for longevity or performance enhancement.
Summary
A study in mice showed that a drug blocking growth‑hormone‑releasing hormone (GH‑RH) called MZ‑4‑71 dramatically shrank kidney cancer tumors by cutting the body’s GH and IGF levels. The compound isn’t available to the public and the research isn’t about sermorelin, so there’s no direct protocol you can use.
Abstract
In view of evidence that growth hormone (GH) and insulin-like growth factors (IGF) may play a role in the development of renal cell carcinoma (RCC), we investigated the effects of growth hormone-releasing hormone (GH-RH) antagonist MZ-4-71 on the proliferation of the human renal adenocarcinoma cell line Caki-I in vitro and in vivo. Male nude mice bearing xenografts of human Caki-I RCC were treated for 4 weeks with MZ-4-71 injected s.c. twice daily at a dose of 20 microg per animal. Tumor growth, serum, liver, and tumor IGF levels and IGF-I receptor concentrations in Caki-I cell membranes were measured. After 4 weeks of therapy, the final volume of Caki-I tumors in nude mice treated with MZ-4-71 was significantly (P < 0.01) decreased to 52.6 +/- 12.3 mm3 as compared with controls that measured 504.2 +/- 104.1 mm3. Treatment with GH-RH antagonist also significantly reduced tumor weight, serum levels of GH and IGF-I, liver concentrations of IGF-I, and tumor levels of IGF-I and IGF-II. High-affinity binding sites for IGF-I were detected in the cell membranes of Caki-I tumors. IGF-I and IGF-II stimulated the proliferation of Caki-I cells in tissue cultures. Antagonist MZ-4-71 could inhibit in vitro growth of Caki-I cells, but only at high concentrations. Our findings demonstrate that GH-RH antagonist MZ-4-71 can significantly inhibit the growth of Caki-I RCC. MZ-4-71 may exert its suppressive effect on tumor growth through a reduction in GH release from the pituitary and the subsequent decrease in the production of IGF-I in the liver and IGF-I and II by the tumors. The efficacy of MZ-4-71 suggests that this compound could be considered for the therapy of recurrent or metastatic RCC.
Study Information
pubmed
1997
1997-05-27T00:00:00.000Z
10.1073/pnas.94.11.5810