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LF-MF 通过激活 P53-miR-34a-E2F1/E2F3 通路抑制铁代谢并抑制肺癌。

LF-MF inhibits iron metabolism and suppresses lung cancer through activation of P53-miR-34a-E2F1/E2F3 pathway.

机构信息

The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China.

Department of Medical Genetics, Nanjing University School of Medicine, Nanjing, 210093, China.

出版信息

Sci Rep. 2017 Apr 7;7(1):749. doi: 10.1038/s41598-017-00913-2.

Abstract

Our previous studies showed that low frequency magnetic fields (LF-MF) suppressed tumor growth and influenced the function of immune system. Nevertheless the mechanisms behind the effect of LF-MF still remain to be elucidated. In this study, Tumor- bearing mice subcutaneously inoculated with Lewis lung cancer cells were exposed to a LF-MF (0.4T, 7.5 Hz) for 35 days and Survival rate, tumor growth and the tumor markers were measured. Results showed that tumor growth was obviously inhibited with a prolonged survival of tumor- bearing mice by LF-MF exposure. In vitro experiments, LF-MF was found to induce cell growth arrest, cell senescence and inhibit iron metabolism of lung cancer cells. Moreover, LF-MF stabilized p53 protein via inhibiting cell iron metabolism and the stabilized p53 protein enhanced miR-34a transcription. Furthermore, increased expression of miR-34a induced cell proliferation inhibition, cell cycle arrest and cell senescence of lung cancer cells by targeting E2F1/E2F3. We also detected the relevant indicator in tumor tissue such as the iron content, the level of miR-34a and related protein, corresponding results were obtained. Taken together, these observations imply that LF-MF suppressed lung cancer via inhibiting cell iron metabolism, stabilizing p53 protein and activation P53- miR-34a-E2F1/E2F3 pathway.

摘要

我们之前的研究表明,低频磁场(LF-MF)抑制肿瘤生长并影响免疫系统的功能。然而,LF-MF 效应背后的机制仍有待阐明。在这项研究中,皮下接种 Lewis 肺癌细胞的荷瘤小鼠接受 LF-MF(0.4T,7.5Hz)照射 35 天,并测量生存率、肿瘤生长和肿瘤标志物。结果表明,LF-MF 照射明显抑制肿瘤生长,延长荷瘤小鼠的生存时间。体外实验发现,LF-MF 诱导肺癌细胞生长停滞、衰老,并抑制铁代谢。此外,LF-MF 通过抑制细胞铁代谢稳定 p53 蛋白,稳定的 p53 蛋白增强 miR-34a 的转录。此外,通过靶向 E2F1/E2F3,增加的 miR-34a 表达抑制肺癌细胞的增殖抑制、细胞周期停滞和衰老。我们还检测了肿瘤组织中的相关指标,如铁含量、miR-34a 水平和相关蛋白,得到了相应的结果。综上所述,这些观察结果表明,LF-MF 通过抑制细胞铁代谢、稳定 p53 蛋白和激活 P53-miR-34a-E2F1/E2F3 通路来抑制肺癌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d3b/5429732/8cc28b3cac23/41598_2017_913_Fig1_HTML.jpg

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