Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Yongin, Republic of Korea.
Biochem Biophys Res Commun. 2012 Jan 6;417(1):521-7. doi: 10.1016/j.bbrc.2011.11.153. Epub 2011 Dec 7.
Alpha-fetoprotein (AFP) is a cancer-associated fetal protein and has long been utilized as a serum fetal defect/tumor marker to monitor distress/disease progression. In addition, AFP is closely associated with the proliferation of hepatocellular carcinoma. Thus, direct targeting of AFP has been recommended for a therapeutic strategy against hepatocellular carcinoma. In this study, we developed and characterized an RNA aptamer that specifically bound to the alpha-fetoprotein using SELEX technology. The aptamer interacted with the AFP with a K(D) of ∼33 nM. Importantly, the identified aptamer specifically and efficiently inhibited the AFP-mediated proliferation of hepatocarcinoma cells in a dose dependent manner. Moreover, the aptamer efficiently down-regulated AFP-induced expression of oncogenes in the cells. These results indicate that an AFP-specific RNA aptamer could be a useful therapeutic and diagnostic agent against AFP-related hepatocellular carcinoma.
甲胎蛋白(AFP)是一种与癌症相关的胎儿蛋白,长期以来一直被用作血清胎儿缺陷/肿瘤标志物,以监测窘迫/疾病进展。此外,AFP 与肝细胞癌的增殖密切相关。因此,直接针对 AFP 已被推荐作为治疗肝细胞癌的一种策略。在这项研究中,我们使用 SELEX 技术开发并鉴定了一种能够特异性结合 AFP 的 RNA 适体。该适体与 AFP 的亲和力常数(K(D))约为 33 nM。重要的是,鉴定出的适体能够特异性和高效地抑制 AFP 介导的肝癌细胞增殖,且具有剂量依赖性。此外,该适体能够有效下调 AFP 诱导的细胞中癌基因的表达。这些结果表明,AFP 特异性 RNA 适体可能是一种对抗 AFP 相关肝细胞癌的有用的治疗和诊断剂。