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

被引：39

作者：

Bellyei, Szabolcs ^{[1
,2
,3
]}

Schally, Andrew V. ^{[1
,2
,3
]}

Zarandi, Marta ^{[1
,2
,3
]}

Varga, Jozsef L. ^{[1
,2
,3
]}

Vidaurre, Irving ^{[1
,2
]}

Pozsgai, Eva ^{[1
,2
,3
]}

机构：

[1] Vet Affairs Med Ctr, Miami, FL 33125 USA

[2] S Florida Vet Affairs Fdn Res & Educ, Miami, FL 33125 USA

[3] Univ Miami, Miller Sch Med, Dept Med, Dept Pathol, Miami, FL 33125 USA

来源：

CANCER LETTERS | 2010年 / 293卷 / 01期

关键词：

GHRH antagonist; Invasion; Metastasis; MMP; NF-kappa B; HORMONE-RELEASING-HORMONE; EPITHELIAL OVARIAN-CANCER; HUMAN PROSTATE-CANCER; NUDE-MICE; SPLICE VARIANTS; KAPPA-B; MATRIX METALLOPROTEINASES; PEPTIDE ANALOGS; DOWN-REGULATION; BREAST CANCERS;

D O I：

10.1016/j.canlet.2009.12.014

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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 upregulation of caveolin-1 and E-cadherin, and the powerful downregulation of NF-kappa B 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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

引用

页码：31 / 40

页数：10

共 62 条

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In vitro targeting of a cytotoxic analog of luteinizing hormone-releasing hormone AN-207 to ES-2 human ovarian cancer cells as demonstrated by microsatellite analyses [J].