Efficiency of ferritin as an MRI reporter gene in NPC cells is enhanced by iron supplementation.

Background. An emerging MRI reporter, ferritin heavy chain (FTH1), is recently applied to enhance the contrast and increase the sensitivity of MRI in the monitoring of solid tumors. However, FTH1-overexpression-related cytotoxicity is required to be explored. Methods. By using the Tet-Off system, FTH1 overexpression was semi-quantitativiely and dynamicly regulated by doxycycline in a NPC cell line. Effects of FTH1 overexpression on the proliferation, cytotoxicity, apoptosis and migration of NPC cells were investigated in vitro, and MR relaxation rate was measured in vitro and in vivo. Results. In vitro and in vivo overexpression of FTH1 significantly increased the transverse relaxivity (R2), which could be enhanced by iron supplementation. In vitro, overexpression of FTH1 reduced cell growth and migration, which were not reduced by iron supplementation. Furthermore, cells were subcutaneously inoculated into the nude mice. Results showed FTH1 overexpression decreased tumor growth in the absence of iron supplementation but not in the presence of iron supplementation. Conclusion. To maximize R2 and minimize the potential adverse effects, supplementation of iron at appropriate dose is recommended during the application of FTH1 as a reporter gene in the monitoring of NPC by MRI.

背景：一种新兴的磁共振成像（MRI）报告基因——铁蛋白重链（FTH1），近期被应用于在实体肿瘤监测中提高MRI的对比度和灵敏度。然而，FTH1过表达相关的细胞毒性需要进行探究。 方法：利用Tet - Off系统，在一种鼻咽癌（NPC）细胞系中，通过强力霉素对FTH1的过表达进行半定量和动态调控。在体外研究FTH1过表达对NPC细胞的增殖、细胞毒性、凋亡和迁移的影响，并在体外和体内测量磁共振弛豫率。 结果：在体外和体内，FTH1过表达显著提高了横向弛豫率（R2），且补铁可增强这一效果。在体外，FTH1过表达降低了细胞生长和迁移能力，且补铁并不能减弱这种作用。此外，将细胞皮下接种到裸鼠体内，结果显示在不补铁的情况下，FTH1过表达会减缓肿瘤生长，但在补铁的情况下则不会。 结论：为了使R2最大化并将潜在不良影响降至最低，在将FTH1作为报告基因应用于MRI监测鼻咽癌时，建议补充适量的铁。