Dose-dependent growth inhibition in vivo of PC-3 prostate cancer with a reduction in tumoral growth factors after therapy with GHRH antagonist MZ-J-7-138.
Heinrich. Elmar E; Schally. Andrew V AV; Buchholz. Stefan S; Rick. Ferenc G FG; Halmos. Gabor G; Mile. Melinda M; Groot. Kate K; Hohla. Florian F; Zarandi. Marta M; Varga. Jozsef L JL
Key Findings
- MZ-J-7-138 reduced prostate tumor size by up to 78% at a dose of 10 µg/day in mice.
- Higher doses of the antagonist significantly lowered tumor levels of IGF‑II and VEGF, proteins that help tumors grow and form blood vessels.
- The drug binds tightly to GHRH receptors on the tumor cells (IC50 = 0.32 nM), confirming a direct target.
Practical Outcomes
- For DIY health enthusiasts, the study suggests that blocking GHRH can curb tumor growth, but it does not provide a usable protocol for humans. It highlights a potential safety concern: long‑term use of GHRH‑stimulating peptides like sermorelin might theoretically have opposite effects on tumor biology, though this study does not test that directly. Until human data are available, the findings are mainly of academic interest rather than a guide for self‑administration.
Summary
In mice with human prostate cancer, a new drug that blocks the hormone that normally tells the pituitary to release growth hormone (a GHRH antagonist called MZ-J-7-138) shrank the tumors in a dose‑dependent way, especially at the highest dose. The drug also lowered two growth‑promoting proteins in the tumors, IGF‑II and VEGF.
Abstract
Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of various cancers and affect tumoral growth factors. We investigated the effect of a new GHRH antagonist MZ-J-7-138 at doses of 1.25, 2.5, 5 and 10 microg/day s.c. on the growth of PC-3 human androgen independent prostate cancers xenografted s.c. into nude mice. Binding assays were used to investigate GHRH receptors. The levels of IGF-II and VEGF in tumors were measured by radioimmunoassays. Treatment with 2.5, 5, and 10 microg/day MZ-J-7-138 caused a significant dose-dependent growth reduction of PC-3 tumors. The greatest inhibition of 78% was obtained with 10 microg/day. The suppression of IGF-II protein levels in tumors was seen at all doses of MZ-J-7-138, but only 10 microg dose induced a significant inhibition. MZ-J-7-138 also reduced VEGF protein levels, the inhibition being significant at doses of 5 and 10 microg. Specific high affinity binding sites for GHRH were found on PC-3 tumors using (125)I-labeled GHRH antagonist JV-1-42. MZ-J-7-138 displaced radiolabeled JV-1-42 with an IC(50) of 0.32 nM indicating its high affinity to GHRH receptors. Real-time PCR analyses detected splice variant 1 (SV1) of GHRH receptor (GHRH-R) as well as pituitary type of GHRH-R and GHRH ligand. Our results demonstrate the efficacy of GHRH antagonist MZ-J-7-138 in suppressing growth of PC-3 prostate cancer at doses lower than previous antagonists. The reduction of levels of growth factors such as VEGF and IGF-II in tumors by GHRH antagonist was correlated with the suppression of tumor growth.
Study Information
pubmed
2008
2008-12-01T00:00:00.000Z
10.1002/pros.20843