Antagonists of growth hormone releasing hormone (GHRH) and of bombesin/gastrin releasing peptide (BN/GRP) suppress the expression of VEGF, bFGF, and receptors of the EGF/HER family in PC-3 and DU-145 human androgen-independent prostate cancers.
Stangelberger. Anton A; Schally. Andrew V AV; Varga. Jozsef L JL; Hammann. Brian D BD; Groot. Kate K; Halmos. Gabor G; Cai. Ren-Zhi RZ; Zarandi. Marta M
Key Findings
- GHRH and BN/GRP antagonists reduced tumor size in two prostate cancer models.
- These antagonists lowered tumor levels of VEGF, bFGF, and some EGF/HER receptors.
- Combining a GHRH antagonist (MZ-J-7-118) with a BN/GRP antagonist (RC-3940-II) gave the strongest tumor‑growth inhibition.
Practical Outcomes
- The results suggest that blocking GHRH signaling may have anti‑cancer effects, but they do not provide actionable advice for using sermorelin, which works in the opposite direction. For biohackers, this study mainly serves as a caution that manipulating the GHRH pathway could have complex effects on tumor biology, and more research is needed before applying any dosage changes.
Summary
In mice with prostate cancer, drugs that block the hormone that normally tells the body to release growth hormone (GHRH) and a related peptide (BN/GRP) slowed tumor growth and lowered levels of several growth‑promoting proteins. The study does not involve sermorelin, which is a GHRH‑activating peptide, so it offers little direct guidance for people using sermorelin for health or longevity.
Abstract
Antagonists of growth hormone releasing hormone (GHRH) as well as antagonists of bombesin/gastrin releasing peptide (BN/GRP) inhibit the growth of various malignancies (cancers) including prostate cancer. We investigated the effects of GHRH antagonists MZ-J-7-118 and RC-J-29-18, BN/GRP antagonists RC-3940-II and RC-3940-Et and the combination of MZ-J-7-118 and RC-3940-II on the growth of PC-3 and DU-145 human androgen independent prostate cancers xenografted s.c. into nude mice. To elucidate the mechanisms of action of these analogs, growth factors like IGF-II (insulin-like growth factor-II), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and epidermal growth factor receptor/human epidermal growth factor receptor (EGF-R/HER) family were measured in tumors as well as IGF-I in serum. Antagonists of GHRH and BN/GRP alone or in combination significantly inhibited growth of PC-3 and DU-145 tumors, the greatest inhibition of tumor volume being achieved by combination of MZ-J-7-118 (5 microg/day) and RC-3940-II (10 microg/day). BN/GRP and GHRH antagonists and their combination also decreased the expression of VEGF significantly in PC-3 and non-significantly in DU-145, as measured by radioimmunoassay for VEGF protein and RT-PCR for mRNA levels of VEGF. GHRH and BN/GRP antagonists reduced bFGF concentrations and the maximal binding capacity of EGF receptors, and their mRNA levels in PC-3 and DU-145 tumors. mRNA levels for HER-2 and -3 were also diminished in PC-3 tumors by GHRH and BN/GRP antagonists. No changes in HER-4 were found after treatment. Serum IGF-I and tumoral IGF-II levels were not affected by the analogs. BN/GRP and GHRH antagonists inhibit growth of PC-3 and DU-145 prostate cancers by suppressing the expression of tumoral growth factors such as VEGF and bFGF as well as the receptors for EGF and related HER-2 and -3. Additive effects on tumor inhibition (TI) in vivo, but not on VEGF, bFGF, or members of the EGF/HER receptor family, can be achieved by the joint administration of both classes of analogs.
Study Information
pubmed
2005
2005-08-01T00:00:00.000Z
10.1002/pros.20262
48
60