Université Paris-Est, Créteil, France.
Cancer Res. 2011 May 1;71(9):3296-305. doi: 10.1158/0008-5472.CAN-10-3459. Epub 2011 Mar 17.
Recent studies have implicated the involvement of cell surface forms of nucleolin in tumor growth. In this study, we investigated whether a synthetic ligand of cell-surface nucleolin known as N6L could exert antitumor activity. We found that N6L inhibits the anchorage-dependent and independent growth of tumor cell lines and that it also hampers angiogenesis. Additionally, we found that N6L is a proapoptotic molecule that increases Annexin V staining and caspase-3/7 activity in vitro and DNA fragmentation in vivo. Through affinity isolation experiments and mass-spectrometry analysis, we also identified nucleophosmin as a new N6L target. Notably, in mouse xenograft models, N6L administration inhibited human tumor growth. Biodistribution studies carried out in tumor-bearing mice indicated that following administration N6L rapidly localizes to tumor tissue, consistent with its observed antitumor effects. Our findings define N6L as a novel anticancer drug candidate warranting further investigation.
最近的研究表明，核仁素的细胞表面形式参与了肿瘤的生长。在这项研究中，我们研究了一种称为 N6L 的已知的核仁素细胞表面的合成配体是否具有抗肿瘤活性。我们发现 N6L 抑制了肿瘤细胞系的锚定依赖性和非依赖性生长，并且还阻碍了血管生成。此外，我们发现 N6L 是一种促凋亡分子，它增加了体外 Annexin V 染色和 caspase-3/7 活性，并在体内导致 DNA 片段化。通过亲和分离实验和质谱分析，我们还鉴定出核磷蛋白是 N6L 的一个新靶点。值得注意的是，在小鼠异种移植模型中，N6L 的给药抑制了人肿瘤的生长。在荷瘤小鼠中进行的生物分布研究表明，给药后 N6L 迅速定位到肿瘤组织，与观察到的抗肿瘤作用一致。我们的研究结果将 N6L 定义为一种新型的抗癌药物候选物，值得进一步研究。
