Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea,
Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea,
Int J Nanomedicine. 2019 Mar 7;14:1779-1787. doi: 10.2147/IJN.S189738. eCollection 2019.
This study was designed to explore a novel approach for transferring NIS protein to cells using extracellular vesicle (EV) and enhancing iodine avidity in hepatocellular carcinoma (HCC) cells.
We transfected the HCC cells (Huh7) with NIS gene, designated as Huh7/NIS, and isolated the EVs from them. Presence of NIS protein in EVs and EV-mediated transport of NIS protein to recipient Huh7 cells were tested using Western blotting. We also examined radioiodine uptake in Huh7 cells treated with EV-Huh7/NIS.
Successful transfer of NIS protein into Huh7 cells was confirmed by WB and microscopy. EVs showed high levels of NIS protein in them. Treatment of Huh7 cells with EV-Huh7/NIS increased the NIS protein level and enhanced I uptake in recipient Huh7 cells. In addition, EV-huh7/NIS pre-treatment enhanced the cytotoxicity of I therapy against Huh7 cells by inducing increased DNA damage/increased γH2A.X foci formation.
This is the first-of-its-kind demonstration of successful transportation of the NIS protein to cells via EVs, which increased radioiodine uptake. This approach can revert radioiodine-resistant cancers into radioiodine-sensitive cancers.
本研究旨在探索一种利用细胞外囊泡（EV）将 NIS 蛋白转移到细胞内并增强肝癌（HCC）细胞碘摄取能力的新方法。
我们将 NIS 基因转染到 HCC 细胞（Huh7）中，命名为 Huh7/NIS，并从中分离 EV。使用 Western blot 检测 EV 中的 NIS 蛋白和 EV 介导的 NIS 蛋白向受体 Huh7 细胞的转运。我们还检查了用 EV-Huh7/NIS 处理的 Huh7 细胞中的放射性碘摄取。
WB 和显微镜证实了 NIS 蛋白成功转移到 Huh7 细胞中。EV 中含有高水平的 NIS 蛋白。用 EV-Huh7/NIS 处理 Huh7 细胞增加了 NIS 蛋白水平并增强了受体 Huh7 细胞对碘的摄取。此外，EV-huh7/NIS 预处理通过诱导增加的 DNA 损伤/增加的 γH2A.X 焦点形成，增强了 I 治疗对 Huh7 细胞的细胞毒性。
这是首次通过 EV 成功将 NIS 蛋白运输到细胞内并增加放射性碘摄取的研究。这种方法可以将放射性碘耐药的癌症转化为放射性碘敏感的癌症。
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