LiCl Treatment Induces Programmed Cell Death of Schwannoma Cells through AKT- and MTOR-Mediated Necroptosis
LiCl Treatment Induces Programmed Cell Death of Schwannoma Cells through AKT- and MTOR-Mediated Necroptosis
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LiCl 治疗通过 AKT 和 MTOR 介导的坏死性凋亡诱导神经鞘瘤细胞程序性细胞死亡
DOI：
10.1007/s11064-017-2256-2
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发表时间：
2017
影响因子：
4.4
通讯作者：
Liu P
中科院分区：
文献类型：
--
作者：
Wang Ying;Zhang Qi;Liu Pinan;Wang Bo;Li Peng;Liu Pinan;Liu P;Liu P
锂被认为是治疗双相情感障碍的一线疗法，最近被证明与降低整体癌症风险有关。越来越多的证据表明这种药物具有潜在的抗肿瘤益处。锂可能作为一种抗肿瘤剂。在这项研究中，我们发现氯化锂（LiCl）显着抑制RT 4细胞和人NF 2相关的原发性神经鞘瘤细胞的增殖，通过抑制凋亡相关蛋白的表达。LiCl诱导的细胞死亡表现出坏死的超微结构特征，并被RIPK 1特异性抑制剂necrostatin-1以剂量依赖性方式逆转，表明LiCl诱导了坏死性凋亡类型的细胞死亡。此外，LiCl处理诱导ROS产生并激活AKT/mTOR通路，其被坏死抑素-1处理逆转。基于我们的研究结果，LiCl处理可能通过AKT和mTOR介导的坏死性凋亡诱导神经鞘瘤细胞的程序性细胞死亡，这可能代表了LiCl诱导肿瘤细胞死亡的新机制。此外，LiCl可能被证明是一种治疗神经鞘瘤的新药。
Lithium is considered a first-line therapy for the treatment of bipolar disorder and was recently shown to be associated with a reduced overall cancer risk. A growing body of evidence has indicated the potential antitumor benefits of this drug. Lithium likely functions as an antitumor agent. In this study, we found that lithium chloride (LiCl) significantly inhibits the proliferation of both RT4 cells and human NF2-associated primary schwannoma cells by inhibiting the expression of apoptosis-related proteins. LiCl-induced cell death exhibits ultrastructural features of necrosis and is reversed by the RIPK1-specific inhibitor necrostatin-1 in a dose-dependent manner, indicating that LiCl induces the necroptosis type of cell death. Moreover, LiCl treatment induces ROS generation and activates the AKT/mTOR pathway, which is reversed by necrostatin-1 treatment. Based on our results, LiCl treatment may induce the programmed cell death of schwannoma cells through AKT- and mTOR-mediated necroptosis, potentially representing a new mechanism by which LiCl induces tumor cell death. Moreover, LiCl may prove to be a new drug for treating schwannoma.