Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D Peptide

整合素 血管生成 癌症研究 受体 生物 细胞生物学 细胞粘附 体外 细胞生长 细胞 化学 生物化学
作者
Domenica Capasso,Annarita Del Gatto,Daniela Comegna,L. Russo,Roberto Fattorusso,Michele Saviano,Sonia Di Gaetano,Laura Zaccaro
出处
期刊:Molecules [MDPI AG]
卷期号:25 (18): 4298-4298 被引量:7
标识
DOI:10.3390/molecules25184298
摘要

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.
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