1 T moderate intensity static magnetic field affects Akt/mTOR pathway and increases the antitumor efficacy of mTOR inhibitors in CNE-2Z cells

Abstract

Static magnetic field (SMF) has been known to affect cell proliferation in a cell-type-dependent manner, while the mechanism still remains unclear. We found that 1 T moderate intensity SMF inhibits cell proliferation of nasopharyngeal carcinoma CNE-2Z cells and the Akt/mTOR signaling pathway, which is upregulated in many cancers. mTOR inhibitors are potential chemodrugs, but their clinical effects are limited by the feedback reactivation of other signaling components such as EGFR and Akt. We showed that 1 T SMF increases the antitumor efficacy of mTOR inhibitor Torin 2. In addition, 1 T SMF increases the inhibition efficiency on mTOR substrates phosphorylation and represses the mTOR inhibitor-induced feedback reactivation of EGFR and Akt. Our study not only demonstrates that mTOR/Akt pathway is one of the molecular targets of SMFs in cells, but also reveals the clinical potentials of combinations of mTOR inhibitors and SMFs in cancer treatment.

摘要

已有报道表明,稳态磁场能够影响细胞分裂,且与细胞类型相关,但其机制并不清楚。我们发现1 T中等强度稳态磁场能够抑制鼻咽癌CNE-2Z细胞的增殖和Akt/mTOR信号通路。Akt/mTOR通路在多种肿瘤中高度活化,因此,mTOR抑制剂是具有潜在应用价值的化疗药物。然而,由于使用过程中出现了其他信号分子如EGFR和AKT的负反馈重新激活,使得这类抑制剂的临床效果受到限制。我们发现1 T稳态磁场能够增强mTOR抑制剂Torin 2的抑瘤效果。生化实验结果表明,1 T稳态磁场不仅增强了Torin 2对mTOR底物磷酸化的抑制,而且减弱了mTOR抑制剂诱导的EGFR和Akt的负反馈重激活。因此,我们的研究不仅证明了mTOR/Akt信号通路是稳态磁场作用于细胞的分子靶点之一,而且揭示了mTOR抑制剂和稳态磁场联合在肿瘤治疗方面的潜在应用。