Electroporation as a strategy to improve the efficacy of chemotherapy in neuroblastoma: an in vitro study.
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BACKGROUND: Reversible electroporation involves the use of pulsed electric fields to temporarily disrupt and permeabilise cell membranes. Electroporation combined with chemotherapy - electrochemotherapy (ECT) - increases tumour cell permeability to chemotherapeutic drugs and enhances their effect. We investigated the efficacy of electroporation and cisplatin as a treatment for neuroblastoma in vitro, and explored whether inhibition of DNA repair mechanisms with olaparib potentiates its effects. MATERIALS AND METHODS: Three immortalised neuroblastoma cell lines were exposed to eight 1 ms square wave pulses of 0-0.93 kV/cm electric fields in the presence of propidium iodide and reversible electroporation was identified by detecting live propidium iodide positive cells by flow cytometry. Intracellular cisplatin and olaparib levels after electroporation were investigated by measuring intracellular platinum via inductively coupled plasma mass spectrometry and by quantifying a fluorescent olaparib with flow cytometry. Cells were exposed to electroporation in the presence of cisplatin and olaparib, and cell death was quantified by flow cytometry. Presence of DNA damage was evaluated by quantifying γ-H2AX immunofluorescence. RESULTS: Reversible electroporation (0.74 kV/cm) increased intracellular cisplatin and olaparib levels. Electroporation with cisplatin (1-100 μM) significantly reduced cell viability compared to cisplatin treatment in all cell lines. The addition of olaparib (5 μM) modestly potentiated the effects of cisplatin and electroporation. DNA damage was significantly higher following treatment with a combination of electroporation, cisplatin and olaparib, compared to each treatment alone. CONCLUSIONS: Electroporation with cisplatin appears effective against neuroblastoma in vitro. Further work will investigate the efficacy of electroporation with cisplatin using clinical ECT devices.