Department of Spine Surgery, Affiliated Longhua People's Hospital, Southern Medical University (Longhua People's Hospital), Shenzhen, China; School of Life Sciences, Northwestern Polytechnical University, Xi'an, China.
School of Life Sciences, Northwestern Polytechnical University, Xi'an, China; Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, 518057, China.
Exp Cell Res. 2022 Aug 15;417(2):113223. doi: 10.1016/j.yexcr.2022.113223. Epub 2022 May 25.
Many studies indicated that static magnetic fields (SMFs) have anti-cancer effects. However, effect of SMFs on cancer cells with strength exceeding 12 T are rarely reported. The intracellular iron could participate in the reactive oxygen species (ROS) production and affect cell proliferation. This study aimed to investigate the effect of 12 T high static magnetic field (HiSMF) on osteosarcoma cells and the relationship with intracellular iron. The 12 T HiSMF was generated by a superconducting magnet. The proliferation was evaluated by CCK-8 assays and cell counting. The apoptosis, cell cycle distribution, and ROS were evaluated by flow cytometry. Intracellular iron status was evaluated by atomic absorption spectroscopy and Calcein-AM/2,2'-bipyridyl. The expression of cell cycle and iron metabolism-related genes were analyzed by Western Blot. The result showed that 12 T HiSMF exposure suppressed the proliferation of osteosarcoma cell lines MNNG/HOS, U-2 OS, and MG63 via cell cycle arrest in S and G2/M. Meanwhile, 12 T HiSMF increasing intracellular ROS, and its antitumor effect was reduced by antioxidant. Furthermore, the intracellular total and free iron levels, the expression of FTH1 and DMT1 were increased by 12 HiSMF. The iron chelator (DFO) could reduce the cytotoxicity of 12 T HiSMF on osteosarcoma cells. Moreover, 12 T HiSMF could enhance the cytotoxicity of cisplatin and sorafenib in osteosarcoma cells. In Conclusion, 12 T HiSMF could suppress osteosarcoma cells proliferation via intracellular iron and ROS related cell cycle arrest, and have application potential in osteosarcoma therapy combined with sorafenib and cisplatin.
许多研究表明静磁场（SMFs）具有抗癌作用。然而，强度超过 12 T 的静磁场对癌细胞的影响很少有报道。细胞内铁可以参与活性氧（ROS）的产生，并影响细胞增殖。本研究旨在探讨 12 T 高静磁场（HiSMF）对骨肉瘤细胞的影响及其与细胞内铁的关系。12 T HiSMF 由超导磁体产生。通过 CCK-8 测定和细胞计数评估增殖。通过流式细胞术评估细胞凋亡、细胞周期分布和 ROS。通过原子吸收光谱法和 Calcein-AM/2,2'-联吡啶评估细胞内铁状态。通过 Western Blot 分析细胞周期和铁代谢相关基因的表达。结果表明，12 T HiSMF 暴露通过细胞周期阻滞在 S 和 G2/M 抑制骨肉瘤细胞系 MNNG/HOS、U-2 OS 和 MG63 的增殖。同时，12 T HiSMF 增加了细胞内 ROS，抗氧化剂可降低其抗肿瘤作用。此外，12 HiSMF 增加了细胞内总铁和游离铁水平、FTH1 和 DMT1 的表达。铁螯合剂（DFO）可降低 12 T HiSMF 对骨肉瘤细胞的细胞毒性。此外，12 T HiSMF 可增强骨肉瘤细胞中顺铂和索拉非尼的细胞毒性。总之，12 T HiSMF 可通过细胞内铁和 ROS 相关的细胞周期阻滞抑制骨肉瘤细胞增殖，并在与索拉非尼和顺铂联合治疗骨肉瘤方面具有应用潜力。
