Low levels of radiofrequency electromagnetic fields and cancer cell proliferation in vivo.

Abstract

e15049 Background: The incidence of hepatocellular carcinoma (HCC) is increasing but five-year survival remains dismal. Intrabuccal administration of amplitude-modulated radiofrequency electromagnetic fields (RF EMF) is a novel, non-invasive treatment modality resulting in whole body absorption of very low levels of RF EMF. Recent studies show that this approach elicits radiological responses in patients with HCC and breast cancer (J Exp Clin Cancer Res, 2009, 28:51; Br J Cancer, 2011, 105:640). Using an in vitro exposure system replicating the levels of exposure achieved in humans, we have shown that HCC cells and breast cancer cells are growth inhibited by HCC-specific and breast cancer-specific frequencies, respectively. Additionally, RF EMF exposure causes modulation of gene expression and disruption of the mitotic spindle (Br J Cancer 2012, 106:307). Methods: HCC cells were exposed to radiofrequency electromagnetic fields modulated at specific frequencies previously identified in HCC patients. MicroRNA arrays compared exposed and control groups of HCC cells. HCC cells were injected subcutaneously in NOD SCID mice. Following palpable tumor establishment, mice were exposed to HCC-specific RF EMF at a specific absorption rate of 0.4 W/kg and euthanized following excessive tumor burden. Results: We identified increased levels of miRNAs targeting proteins belonging to the PI3K pathway, specifically IP3/DAG signaling and intracellular calcium release, a pathway frequently disrupted in HCC and breast cancer. While HCC xenografts grew in control mice, we observed significant tumor shrinkage in mice exposed to HCC-specific modulation frequencies and residual xenograft tumor cells were infiltrated with fibrous tissue and showed significantly decreased proliferation and increased apoptosis. There was no evidence of altered cell proliferation or fibrosis in other organs. Conclusions: These findings are the first in vivo evidence of the efficacy of RF EMF in HCC and uncover a novel mechanism that targets cancer cell growth at specific modulation frequencies, by means of changes in PI3K signaling and release of intracellular calcium.