Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education, Miami, FL 33125, USA.
Cancer Lett. 2010 Jul 1;293(1):31-40. doi: 10.1016/j.canlet.2009.12.014. Epub 2010 Jan 12.
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.
我们研究了 GHRH 拮抗剂 MIA-602 对三种人类癌症（胶质母细胞瘤 DBTRG-05、雌激素非依赖性乳腺癌 MDA-MB-468 和透明细胞卵巢癌 ES-2）体外转移级联的影响。在所有三种细胞系上均检测到 GHRH 受体及其主要剪接变体 SV1。用 MIA-602 处理后，细胞活力显著下降，观察到细胞侵袭显著抑制，MMPs 的释放显著减少。癌细胞对纤维连接蛋白和基质胶的附着受到严重阻碍。划痕实验表明，所有三种细胞系的细胞迁移能力均降低。检测到 caveolin-1 和 E-cadherin 的上调，以及 NF-kappaB 和 beta-catenin 的强力下调。我们的研究表明，在癌症治疗中临床应用高活性 GHRH 拮抗剂是可取的，因为它们既抑制增殖又抑制转移发展。
