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

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.