The study tested two experimental drugs that block growth‑hormone‑releasing hormone (GHRH) and found they slowed the growth of lung‑cancer cells in petri dishes and in mice. These compounds are not the same as sermorelin, which is a GHRH‑activating peptide, and the work is still far from any human use.

We investigated the effects of novel antagonists of growth hormone releasing hormone (GHRH)-MIA602 and MIA690-on three human small cell lung cancer (SCLC) lines (H446, DMS53 and H69) and two non-SCLC (NSCLC) lines (HCC827 and H460). In vitro exposure of cancer cells to these GHRH antagonists significantly inhibited cell viability, increased cell apoptosis, decrease cellular levels of cAMP and reduced cell migration. In vivo, the antagonists strongly inhibited tumor growth in xenografted nude mice models. Subcutaneous administration of MIA602 at the dose of 5 μg/day for 4-8 weeks reduced the growth of HCC827, H460 and H446 tumors by 69.9%, 68.3% and 53.4%, respectively, while MIA690 caused a reduction of 76.8%, 58.3% and 54.9%, respectively. Western blot and qRT-PCR analyses demonstrated a downregulation of expression of the pituitary-type GHRH-R and its splice-variant, cyclinD1/2, cyclin-dependent kinase4/6, p21-activated kinase-1, phosphorylation of activator of transcription 3 and cAMP response element binding protein; and an upregulation of expression of E-cadherin, β-catenin and P27^kip1 in cancer cells and in xenografted tumor tissues. The study demonstrates the involvement of GHRH antagonists in multiple signaling pathways in lung cancers. Our findings suggest the merit of further investigation with these GHRH antagonists on the management of both SCLC and NSCLC.