CESTEV, University of Naples "Federico II", 80145 Naples, Italy.
CIRPeB, University of Naples "Federico II", 80134 Naples, Italy.
Molecules. 2020 Sep 19;25(18):4298. doi: 10.3390/molecules25184298.
Recently, the research community has become increasingly concerned with the receptor αvβ5, a member of the well-known integrin family. Different ongoing studies have evidenced that αvβ5 integrin regulates not only physiological processes but also a wide array of pathological events, suggesting the receptor as a valuable biomarker to specifically target for therapeutic/diagnostic purposes. Remarkably, in some tumors the involvement of the receptor in cell proliferation, tumor dissemination and angiogenesis is well-documented. In this scenario, the availability of a selective αvβ5 antagonist without 'off-target' protein effects may improve survival rate in patients with highly aggressive tumors, such as hepatocellular carcinoma. We recently reported a cyclic peptide, RGDechi15D, obtained by structure-activity studies. To our knowledge it represents the first peptide-based molecule reported in the literature able to specifically bind αvβ5 integrin and not cross react with αvβ3. Here we demonstrated the ability of the peptide to diminish both adhesion and invasion of HepG2 cells, an in vitro model system for hepatocellular carcinoma, to reduce the cell proliferation through an apoptotic process, and to interfere with the PI3K pathway. The peptide, also decreases the formation of new vessels in endothelial cells. Taken together these results indicate that the peptide can be considered a promising molecule with properties suited to be assessed in the future for its validation as a selective therapeutic/diagnostic weapon in hepatocarcinoma.
最近，研究界越来越关注细胞表面受体αvβ5，它是众所周知的整合素家族的一员。不同的研究表明，αvβ5 整合素不仅调节生理过程，还调节广泛的病理事件，这表明该受体是一种有价值的生物标志物，可专门用于治疗/诊断目的。值得注意的是，在一些肿瘤中，受体在细胞增殖、肿瘤扩散和血管生成中的作用已得到充分证实。在这种情况下，使用无“脱靶”蛋白效应的选择性αvβ5 拮抗剂可能会提高高侵袭性肿瘤（如肝细胞癌）患者的生存率。我们最近报道了一种通过结构活性研究获得的环状肽 RGDechi15D。据我们所知，它是文献中首次报道的能够特异性结合 αvβ5 整合素而不与 αvβ3 交叉反应的肽类分子。在这里，我们证明了该肽能够减少 HepG2 细胞的黏附和侵袭，HepG2 细胞是肝细胞癌的体外模型系统，通过凋亡过程减少细胞增殖，并干扰 PI3K 途径。该肽还可减少内皮细胞中新血管的形成。综上所述，这些结果表明，该肽可以被认为是一种有前途的分子，具有适合在未来作为选择性治疗/诊断武器在肝癌中进行验证的特性。
