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利用针对 MCF-7 细胞筛选的 DNA 适体区分乳腺癌分子亚型。

Differentiating breast cancer molecular subtypes using a DNA aptamer selected against MCF-7 cells.

机构信息

State Key Laboratory of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education (Southeast University), School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, P. R. China.

出版信息

Biomater Sci. 2018 Nov 20;6(12):3152-3159. doi: 10.1039/c8bm00787j.

Abstract

Aptamers are single-stranded DNA or RNA oligonucleotides selected by systematic evolution of ligands by exponential enrichment (SELEX), which show great potential in the diagnosis and personalized therapy of cancers, due to their specific advantages over antibodies. In the past years, though great progress has been made in molecular subtyping of breast cancer, it remains a challenge in clinical medicine, which plays a crucial role in the treatment. In this study, a ssDNA aptamer MF3 against MCF-7 breast cancer cells was developed by Cell-SELEX for differentiating breast cancer molecular subtypes, which showed favorable specificity and binding affinity towards MCF-7 cells with a Kd value of 82.25 ± 25.14 nM. The aptamer could not only successfully distinguish MCF-7 breast cancer cells from MDA-MB-231 and SK-BR-3 breast cancer cells and MCF-10A human normal mammary epithelial cells, but also could differentiate MCF-7 cells from other cancer cells or normal cells. Moreover, both in vivo and in vitro fluorescence imaging studies demonstrated that aptamer MF3 was able to distinguish tumor-bearing mice and xenograft tissue sections of MCF-7 breast cancer cells from that of MDA-MB-231 and SK-BR-3 breast cancer cells. All these results suggested that aptamer MF3 is a potential tool for differentiating molecular subtypes and diagnosis of breast cancer.

摘要

适配体是通过指数富集的配体系统进化(SELEX)筛选出的单链 DNA 或 RNA 寡核苷酸,由于其优于抗体的特定优势,在癌症的诊断和个性化治疗中具有巨大潜力。尽管在过去的几年中,乳腺癌的分子亚型分类取得了很大进展,但在临床医学中仍然是一个挑战,这在治疗中起着至关重要的作用。在这项研究中,通过细胞 SELEX 开发了针对 MCF-7 乳腺癌细胞的 ssDNA 适配体 MF3,用于区分乳腺癌分子亚型,其对 MCF-7 细胞表现出良好的特异性和结合亲和力,Kd 值为 82.25 ± 25.14 nM。该适配体不仅能够成功区分 MCF-7 乳腺癌细胞与 MDA-MB-231 和 SK-BR-3 乳腺癌细胞和 MCF-10A 人正常乳腺上皮细胞,还能够区分 MCF-7 细胞与其他癌细胞或正常细胞。此外,体内和体外荧光成像研究表明,适配体 MF3 能够区分荷瘤小鼠和 MCF-7 乳腺癌细胞的异种移植组织切片与 MDA-MB-231 和 SK-BR-3 乳腺癌细胞的异种移植组织切片。所有这些结果表明,适配体 MF3 是区分分子亚型和诊断乳腺癌的潜在工具。

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