GHRH Antagonists Show Promise Against Prostate Cancer Growth and Spread

Prostate cancer remains a significant global health challenge, with advanced stages often proving difficult to treat effectively. Current therapies frequently face limitations in preventing tumor growth and metastatic spread. This study addresses a critical knowledge gap by investigating whether targeting the Growth Hormone-Releasing Hormone (GHRH) pathway with specific antagonists can inhibit the proliferation and invasiveness of human prostate cancer cells.

In vitro, both MZ-4-71 and MZ-J-7-106 significantly inhibited PC3 cell proliferation in a dose-dependent manner. Specifically, MZ-4-71 at 100 nM reduced cell numbers by 43% after 48 hours (p<0.01), while also inducing apoptosis (programmed cell death) and decreasing cell invasiveness by 50% (p<0.01). The antagonists also reduced the expression of GHRH receptors on the cancer cells. > In vivo, treatment with MZ-4-71 at 10 µg/day for 28 days resulted in a remarkable 60% reduction in PC3 prostate cancer tumor volume and a 55% reduction in tumor weight compared to controls (p<0.01 for both). The lower dose of 5 µg/day also showed significant reductions of 50% in tumor volume and 45% in tumor weight (p<0.01). Furthermore, the antagonists significantly reduced the expression of VEGF (Vascular Endothelial Growth Factor, a protein that promotes new blood vessel growth) and IGF-1 (Insulin-like Growth Factor 1), both crucial for tumor growth and angiogenesis.