Antagonists of growth hormone-releasing hormone (GH-RH) inhibit in vivo proliferation of experimental pancreatic cancers and decrease IGF-II levels in tumours.
Szepeshazi. K K; Schally. A V AV; Groot. K K; Armatis. P P; Hebert. F F; Halmos. G G
Key Findings
- GH‑RH antagonists (MZ‑4‑71 and MZ‑5‑156) reduced tumor weight and size in hamster and mouse models of pancreatic cancer.
- Tumor IGF‑II levels dropped by about 50‑60% after treatment, suggesting the drugs lower cancer‑driven IGF‑II production.
- In cell culture, the antagonist lowered cancer cell proliferation, IGF‑II mRNA, and secreted IGF‑II.
Practical Outcomes
- For most biohackers, this study offers little direct guidance because it investigates GH‑RH blockers—not the GH‑RH agonist sermorelin that many use for anti‑aging. The findings hint that suppressing GH‑RH could have anti‑cancer effects via IGF‑II reduction, but such compounds are experimental and not ready for self‑administration.
Summary
In animal studies, drugs that block the hormone that normally tells the pituitary to release growth hormone (GH‑RH antagonists) shrank pancreatic tumors and cut the amount of a growth‑promoting protein called IGF‑II inside the tumors, while leaving IGF‑I unchanged.
Abstract
Insulin-like growth factors (IGF-I and IGF-II) are implicated in the pathogenesis of pancreatic carcinoma. Antagonists of growth hormone-releasing hormone (GH-RH) suppress the GH-RH-GH-IGF-I axis and also act directly on tumours to reduce production of IGF-I or II. The aim of this study was to investigate the effects of two potent GH-RH antagonists in two experimental models of pancreatic cancer. Syrian golden hamsters with nitrosamine-induced pancreatic tumours were treated with 10 micrograms/day of GH-RH antagonist MZ-4-71 for 60 days. The therapy reduced the number of tumorous animals, decreased the weight of tumorous pancreata by 55%, and lowered AgNOR numbers in tumour cells. In two other experiments, GH-RH antagonists MZ-4-71 and MZ-5-156 significantly inhibited growth of SW-1990 human pancreatic cancers xenografted into nude mice, as shown by a reduction in tumour volume and tumour weights, and a decrease in AgNORs in cancer cells. IGF-I levels in serum and in pancreatic cancer tissue remained unchanged after therapy, suggesting that an effect on IGF-I is not involved in tumour inhibition. In contrast, IGF-II concentrations in tumours were significantly reduced by 50-60% after treatment with the GH-RH antagonists as compared with controls. In vitro studies showed that the concentration of IGF-II in the culture medium was increased after seeding of SW-1990 cells, indicating that this pancreatic cancer cell line produced and released IGF-II. This finding was also supported by the expression of IGF-II mRNA in the SW-1990 cells. Addition of 3 x 10(-6) M of GH-RH antagonist MZ-5-156 to the reduced-serum medium decreased cell proliferation, IGF-II mRNA expression in the cells and IGF-II concentration in the medium. Our findings indicate that inhibitory effects of GH-RH antagonists on the growth of experimental pancreatic cancers, may result from a decrease in the production and concentration of IGF-II in the tumours.
Study Information
pubmed
2000
10.1016/s0959-8049(99)00230-0