sermorelin and Small-Cell-Lung-Carcinoma

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

Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Cyclic AMP; Cyclic AMP Response Element-Binding Protein; Disease Models, Animal; Female; Gene Expression; Growth Hormone-Releasing Hormone; Humans; Mice; Mice, Nude; Sermorelin; Signal Transduction; Small Cell Lung Carcinoma; STAT3 Transcription Factor; Xenograft Model Antitumor Assays

Topics: Alternative Splicing; Animals; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Cell Survival; Down-Regulation; Female; Growth Hormone-Releasing Hormone; Humans; Mice; Mice, Nude; Receptors, Neuropeptide; Receptors, Pituitary Hormone-Regulating Hormone; RNA Splicing; Sermorelin; Small Cell Lung Carcinoma; Xenograft Model Antitumor Assays