Selenite Induces Cell Cycle Arrest and Apoptosis via Reactive Oxygen Species-Dependent Inhibition of the AKT/mTOR Pathway in Thyroid Cancer.
Selenite Induces Cell Cycle Arrest and Apoptosis via Reactive Oxygen Species-Dependent Inhibition of the AKT/mTOR Pathway in Thyroid Cancer.
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亚硒酸盐通过活性氧依赖性抑制甲状腺癌中的 AKT/mTOR 途径诱导细胞周期停滞和细胞凋亡
DOI：
10.3389/fonc.2021.668424
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发表时间：
2021
影响因子：
4.7
通讯作者：
Xiao H
中科院分区：
文献类型：
--
作者：
Cheng Z;Yu S;He W;Li J;Xu T;Xue J;Shi P;Chen S;Li Y;Hong S;Xiao H
甲状腺癌是最常见的内分泌恶性肿瘤，其发病率在过去几十年中呈上升趋势。硒已被证明对几种肿瘤有治疗作用。然而，其在甲状腺癌中的作用及其潜在的分子机制仍有待探索。在本研究中，我们证明，亚硒酸钠显着降低细胞活力和诱导G 0/G1期细胞周期阻滞和凋亡的甲状腺癌细胞在剂量依赖性的方式。转录组学研究表明，亚硒酸钠通过促进氧化磷酸化诱导细胞内活性氧（ROS）。增加的细胞内ROS水平抑制AKT/mTOR信号通路并上调EIF 4 EBP 3。N-乙酰半胱氨酸（NAC）抑制细胞内ROS可改善亚硒酸钠的细胞效应。在异种移植甲状腺肿瘤模型中重现了体外结果。我们的数据表明，亚硒酸钠对甲状腺癌细胞具有很强的抗癌作用，这涉及ROS介导的AKT/mTOR通路的抑制。这表明亚硒酸钠可以作为晚期甲状腺癌的治疗选择。
Thyroid cancer is the most common endocrine malignancy, and its incidence has increased in the past decades. Selenium has been shown to have therapeutic effects against several tumors. However, its role in thyroid cancer and its underlying molecular mechanism remains to be explored. In the present study, we demonstrated that sodium selenite significantly decreased cell viability and induced G0/G1 cell cycle arrest and apoptosis in thyroid cancer cells in a dose-dependent manner. Transcriptomics revealed that sodium selenite induced intracellular reactive oxygen species (ROS) by promoting oxidative phosphorylation. Increased intracellular ROS levels inhibited the AKT/mTOR signaling pathway and upregulated EIF4EBP3. Intracellular ROS inhibition by N-acetylcysteine (NAC) ameliorated the cellular effects of sodium selenite. The in vitro findings were reproduced in xenograft thyroid tumor models. Our data demonstrated that sodium selenite exhibits strong anticancer effects against thyroid cancer cells, which involved ROS-mediated inhibition of the AKT/mTOR pathway. This suggests that sodium selenite may serve as a therapeutic option for advanced thyroid cancer.
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