GHRH antagonists reduce the invasive and metastatic potential of human cancer cell lines in vitro

Authors

Szabolcs Bellyei, University of MiamiFollow
Andrew V. Schally, University of Miami
Marta Zarandi, University of Miami
Jozsef L. Varga, University of Miami
Irving Vidaurre, South Florida Veterans Affairs Foundation for Research and Education
Eva Pozsgai, University of MiamiFollow

Date of this Version

2010

Document Type

Article

Citation

Cancer Letters 293 (2010) 31–40; doi:10.1016/j.canlet.2009.12.014

Abstract

We investigated the effect of a GHRH antagonist, MIA-602 on the metastatic cascade in vitro of three human cancers, DBTRG-05 glioblastoma, MDA-MB-468 estrogen-independent breast, and ES-2 clear cell ovarian cancer. GHRH receptors and their main splice variant, SV1 were detected on all three cell lines. After treatment with MIA-602, the cell viability decreased significantly, significant inhibition of cell invasion was observed and the release of MMPs was significantly decreased. The attachment of cancer cells to fibronectin and matrigel was severely hindered. Wound-healing experiments demonstrated a reduced cellular motility in all three cell lines. The up regulation of caveolin-1 and E-cadherin, and the powerful down regulation of NF-ĸB and β-catenin was detected. Our study suggests that the clinical application of highly potent GHRH antagonists in cancer therapy would be desirable since they inhibit proliferation and metastasis development as well.