Siejka A, Ławnicka H, Komorowski J, Schally A V, Stepień T, Krupiński R, Stepień H
Institute of Endocrinology, Medical University of Łódź, 91-425, Sterlinga 3, Łódź, Poland.
Life Sci. 2003 Apr 18;72(22):2473-9. doi: 10.1016/s0024-3205(03)00164-4.
Angiogenesis plays a key role in solid tumor formation, invasiveness and metastasis. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that is necessary in the process of neovascularisation. Antagonists of growth hormone-releasing hormone (GH-RH) have been shown to suppress both in vivo and in vitro growth and metastasis of many human cancer cell lines. The mechanisms that mediate the antitumorigenic actions of these antagonists involve direct and indirect pathways, but are not completely elucidated. We have examined the effect of GH-RH antagonist MZ-4-71 on proliferation activity and VEGF release from cultured murine endothelial cells HECa10 in vitro. MZ-4-71 at 10(-8) to 10(-6) M concentrations inhibited the proliferative activity of cultured cells and suppressed the release of VEGF into supernatants of 72 h endothelial cell cultures. To our knowledge this is the first study reporting antiangiogenic properties of GH-RH antagonists.
血管生成在实体瘤的形成、侵袭和转移过程中起着关键作用。血管内皮生长因子（VEGF）是一种内皮细胞特异性有丝分裂原，在新血管形成过程中必不可少。生长激素释放激素（GH-RH）拮抗剂已被证明在体内和体外均可抑制多种人类癌细胞系的生长和转移。介导这些拮抗剂抗肿瘤作用的机制涉及直接和间接途径，但尚未完全阐明。我们在体外研究了GH-RH拮抗剂MZ-4-71对培养的小鼠内皮细胞HECa10增殖活性和VEGF释放的影响。浓度为10(-8)至10(-6) M的MZ-4-71可抑制培养细胞的增殖活性，并抑制VEGF释放到72小时内皮细胞培养上清液中。据我们所知，这是第一项报道GH-RH拮抗剂具有抗血管生成特性的研究。
