Veterans Affairs Medical Center Education, Miami, FL 33125, USA.
Peptides. 2012 Sep;37(1):63-8. doi: 10.1016/j.peptides.2012.07.010. Epub 2012 Jul 20.
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.
表现出血管生成增加和微血管密度高的肺癌被认为是高度转移性的，预后不良。生长激素释放激素（GHRH）拮抗剂是一种抗癌药物，在肺癌肿瘤模型中没有不良反应。在本研究中，我们研究了 GHRH 拮抗剂 MZ-5-156 对 A549 非小细胞肺癌（NSCLC）癌细胞和 H727 支气管类癌细胞中粘着斑激酶（FAK）活性、MMP-2 和 MMP-9 金属蛋白酶表达以及血管内皮生长因子（VEGF）水平的体外影响。我们首次证明，GHRH 拮抗剂 MZ-5-156 抑制肺癌细胞中的 FAK 信号通路，并降低参与血管生成和侵袭的其他因子的表达。相比之下，GHRH 本身则拮抗了这些作用。我们的研究有助于进一步了解 GHRH 及其拮抗剂在癌症中的作用机制。
