Electroporation enhances chemosensitivity of uveal melanoma cells

Abstract

PurposeElectrochemotherapy (ECT) is increasingly being used for tumour ablation with reduced systemic toxicity, in cancers refractory to current treatments. Metastatic UM is characterised by its innate chemoresistance to many widely used cytotoxic drugs; however, there are no reports of the use of ECT in this disease. We investigated the cytotoxic effect of bleomycin in combination with electroporation on three human uveal melanoma (UM) cell lines in vitro.MethodsMel270, 92‐1 and OMM‐1 UM cell lines were treated with either: a) electroporation alone (pulse amplitude 300–750 V/cm, 8–10 pulses, 100 μs, 5 Hz); b) bleomycin alone (0–10 μg/ml) or; c) in combination. Cell survival was analyzed by MTT viability assay after 36 h.ResultsElectroporation alone reduced cell viability in all UM cell lines with increasing pulse amplitude as compared with untreated control cells; maximum reduction in viability across all UM cell lines was 27% at 750 V/cm for 10 pulses. All UM cell lines were resistant to the cytotoxic effects of bleomycin (0–10 μg/ml) alone. ECT of the UM cell lines with 750 V/cm, 8 pulses, 100 μs, 5 Hz and bleomycin showed a dose‐dependent reduction in cell viability; 1 μg/ml bleomycin reduced viability by 57%, 46% and 51% in the Mel270, 92‐1 and OMM‐1 UM cell lines, respectively.ConclusionsIn vitro ECT with bleomycin was more effective than the highest concentration of the antineoplastic drug or electroporation alone, opening new perspectives in the treatment of UM.