Abstract
Alternating electric fields at an intermediate frequency (100~300 kHz), referred to as tumour-treating fields (TTF), are believed to interrupt the process of mitosis via apoptosis and to act as an inhibitor of cell proliferation. Although the existence of an antimitotic effect of TTF is widely known, the proposed apoptotic mechanism of TTF on cell function and the efficacy of TTF are controversial issues among medical experts. To resolve these controversial issues, a better understanding of the underlying molecular mechanisms of TTF on cell function and the differences between the effects of TTF alone and in combination with other treatment techniques is essential. Here, we report experimental evidence of TTF-induced apoptosis and the synergistic antimitotic effect of TTF in combination with ionizing radiation (IR). For these experiments, two human Glioblastoma multiforme (GBM) cells (U373 and U87) were treated either with TTF alone or with TTF followed by ionizing radiation (IR). Cell apoptosis, DNA damage, and mitotic abnormalities were quantified after the application of TTF, and their percentages were markedly increased when TTF was combined with IR. Our experimental results also suggested that TTF combined with IR synergistically suppressed both cell migration and invasion, based on the inhibition of MMP-9 and vimentin.
Highlights
Glioblastoma multiforme (GBM) is one of the most dangerous cancers, with a poor prognosis
Another randomized clinical trial in newly diagnosed glioblastoma patients has strongly suggested that the use of treating fields (TTF) in combination with chemotherapeutic agents improves the survival rate without a significant increase in toxicity compared with chemotherapy alone [9, 10]
The percentage of cell death in U373 cells (U87) at 72 h after TTF+ionizing radiation (IR) treatment was 23.9 (17.1) %, which was higher than the sum of the percentages of cell death resulting from either TTF or IR alone measured at 72 h after each treatment, which was 9.10 (2.09) % or 6.54 (2.98) % (Figure 1c-1d)
Summary
Glioblastoma multiforme (GBM) is one of the most dangerous cancers, with a poor prognosis. The only randomized clinical trial published in the peer-reviewed literature showed that the outcome for recurrent GBM patients in the TTF group was not distinctly better than that for the conventional therapy group [8]. Another randomized clinical trial in newly diagnosed glioblastoma patients has strongly suggested that the use of TTF in combination with chemotherapeutic agents improves the survival rate without a significant increase in toxicity compared with chemotherapy alone [9, 10]. Previous studies have suggested that the clinical efficacy of TTF alone remains controversial, combination therapy with TTF and chemotherapy is more effective than chemotherapy alone for newly diagnosed GBM patients
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