GHRH antagonist inhibits focal adhesion kinase (FAK) and decreases expression of vascular endothelial growth factor (VEGF) in human lung cancer cells in vitro.

Abstract

Lung cancers which show increased vascularization and high microvessel density are considered highly metastatic and with poor prognosis. Growth hormone releasing hormone (GHRH) antagonists are anticancer agents without adverse events in lung cancer tumor models. In the present study we investigated the in vitro effect of GHRH antagonist, MZ-5-156, on focal adhesion kinase (FAK) activity, on the expression of MMP-2 and MMP-9 metalloproteinases, as well as on vascular endothelial growth factor (VEGF) levels in A549 non-small cell lung (NSCLC) cancer cells and H727 bronchial carcinoid cells. We demonstrate for the first time that GHRH antagonist, MZ-5-156, inhibits FAK signaling in lung cancer cells and decreases the expression of additional factors involved in angiogenesis and invasion. In contrast, GHRH itself counteracted these effects. Our study contributes to the further understanding of the processes which govern the mechanism of action of GHRH and its antagonists in cancers.

• Authors: Agnieszka Siejka, Nektarios Barabutis, Andrew V Schally
• Journal: Peptides (Peptides) Vol. 37 Issue 1 Pg. 63-8 (Sep 2012) ISSN: 1873-5169 [Electronic] United States
• PMID: 22819774 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• MZ 5-156
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Sermorelin
• Growth Hormone-Releasing Hormone
• Focal Adhesion Protein-Tyrosine Kinases
• MMP2 protein, human
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Cell Line, Tumor
• Down-Regulation
• Focal Adhesion Protein-Tyrosine Kinases (antagonists & inhibitors, metabolism)
• Gene Expression
• Growth Hormone-Releasing Hormone (antagonists & inhibitors, physiology)
• Humans
• Lung Neoplasms
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Phosphorylation
• Protein Processing, Post-Translational (drug effects)
• Sermorelin (analogs & derivatives, pharmacology)
• Vascular Endothelial Growth Factor A (genetics, metabolism)