Pulsed electromagnetic field exposure : a novel microwave technique in potential breast cancer treatment

The main objectives of this study are to uncover the potential mechanism of pulsed electromagnetic field exposure (PEFE) at the microwave range in inducing cell death in breast cancer cell lines in vitro and to confirm its clinical significance using a nude mouse model xenografted with human breast cancer cells. This novel technique can potentially contribute to the clinical treatment of breast cancer. A dedicated microwave system was constituted and calibrated for precise PEFE generation and delivery. PEFE induced cell death included necrosis and apoptosis. Necrosis was discovered to be mainly due to the breakdown of membrane structure and cellular organelles, whilst apoptosis was triggered by disruption of tight junctions. The disrupted tight junction of the human breast cancer cells caused an under expression of ZO-1, a key component of the tight junction and HSP90, a heat shock protein involved in cell death. The decreased level of HSP90 activated caspase-dependent apoptotic signalling pathways with the subsequent overexpression of Caspase3/9 inhibiting glycolysis in metabolic signalling pathways, which was confirmed by a series of metabolic assays. Furthermore, a neural regulator, namely Kidins220, was discovered to be a biomarker for PEFE treatments. Increased efficacy of the PEFE treatment was demonstrated in breast cancer cell lines with Kidins220 knockdown. In conclusion, PEFE can exert its efficacy of cell-killing in breast cancer cells, reflecting its potential application in clinical breast cancer treatments. Independent of the thermal effect of microwaves, this minimally invasive technique can be costeffective with less pain and side effects.