GHRH antagonists reduce the invasive and metastatic potential of human cancer cell lines in vitro.
We investigated the effect of a GHRH antagonist, MIA-602on 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 upregulation of caveolin-1 and E-cadherin,and thepowerful downregulation of NF-kappaB and beta-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.
Bellyei
Szabolcs
S
Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education, Miami, FL 33125, USA. bellyeisz@gmail.com <bellyeisz@gmail.com>
Schally
Andrew V
AV
Zarandi
Marta
M
Varga
Jozsef L
JL
Vidaurre
Irving
I
Pozsgai
Eva
E
D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms; D017337:Sermorelin / Q000031:analogs & derivatives* / Q000494:pharmacology
C550121:GHRH(1-29)NH2, (PhAc-Ada)(0)-Tyr(1), Arg(2), Fpa(5,6), Ala(8), Har(9), Tyr(Me)(10), His(11), Orn(12,) Abu(15), His(20), Orn(21), Nle(27), Arg(28), Har(29)-; D020033:Protein Isoforms; D017337:Sermorelin; D013007:Growth Hormone-Releasing Hormone