Core for Medicine and Science Collaborative Research and Education, Forefront Research Center, Osaka University Graduate School of Science, 1-1 Toyonaka, Osaka 560-0043, Japan.
Institute for Radiation Sciences, Osaka University, 2-4 Suita, Osaka 565-0871, Japan.
Int J Mol Sci. 2022 Dec 7;23(24):15509. doi: 10.3390/ijms232415509.
This study confirmed the effect of sodium/iodine symporter (NIS) expression on existing drugs by in vitro and in vivo tests using cultured cell lines. The tumor growth inhibitory effect of sodium astatide ([At]NaAt) was evaluated by in vitro and in vivo tests using human thyroid cancer cells (K1, K1/NIS and K1/NIS-DOX). NIS expression in cancer cells was controlled using the Tet-On system. [I]NaI was used as control existing drug. From the results of the in vitro studies, the mechanism of [At]NaAt uptake into thyroid cancer cells is mediated by NIS, analogous to [I]NaI, and the cellular uptake rate correlates with the expression level of NIS. [At]NaAt's ability to inhibit colony formation was more than 10 times that of [I]NaI per becquerel (Bq), and [At]NaAt's DNA double-strand breaking (DSB) induction was more than ten times that of [I]NaI per Bq, and [At]NaAt was more than three times more cytotoxic than [I]NaI (at 1000 kBq each). In vivo studies also showed that the tumor growth inhibitory effect of [At]NaAt depended on NIS expression and was more than six times that of [I]NaI per Bq.
这项研究通过体外和体内试验，利用培养的细胞系证实了钠/碘同向转运体（NIS）表达对现有药物的影响。通过体外和体内试验，利用人甲状腺癌细胞（K1、K1/NIS 和 K1/NIS-DOX）评估放射性碘酸钠（[At]NaAt）的肿瘤生长抑制作用。使用 Tet-On 系统控制癌细胞中的 NIS 表达。[I]NaI 被用作对照现有药物。从体外研究的结果来看，[At]NaAt 进入甲状腺癌细胞的摄取机制与 NIS 介导的 [I]NaI 类似，细胞摄取率与 NIS 的表达水平相关。[At]NaAt 抑制集落形成的能力比每贝克勒尔（Bq）的 [I]NaI 高出 10 倍以上，[At]NaAt 的 DNA 双链断裂（DSB）诱导比每 Bq 的 [I]NaI 高出 10 倍以上，[At]NaAt 的细胞毒性比 [I]NaI 高出 3 倍以上（各为 1000 Bq）。体内研究还表明，[At]NaAt 的肿瘤生长抑制作用取决于 NIS 的表达，比每 Bq 的 [I]NaI 高出 6 倍以上。
