Differential effects of nanosecond pulsed electric fields on cells representing progressive ovarian cancer

•• Response of progressive ovarian cancer cells to nsPEFs was firstly investigated.•• nsPEFs preferentially target late-stage/ highly aggressive ovarian cancer cells.•• Selective effect of nsPEFs could be contributed by the intracellular effect.•• Cell proliferation does not affect the ablation outcome of differential nsPEF-effects. Nanosecond pulsed electric fields (nsPEFs) may induce differential effects on tumor cells from different disease stages and could be suitable for treating tumors by preferentially targeting the late-stage/highly aggressive tumor cells. In this study, we investigated the nsPEF responses of mouse ovarian surface epithelial (MOSE) cells representing progressive ovarian cancer from benign to malignant stages and highly aggressive tumor-initiating-like cells. We established the cell-seeded 3D collagen scaffolds cultured with or without Nocodazole (eliminating the influence of cell proliferation on ablation outcome) to observe the ablation effects at 3 h and 24 h after treatment and compared the corresponding thresholds obtained by numerically calculated electric field distribution. The results showed that nsPEFs induced larger ablation areas with lower thresholds as the cell progress from benign, malignant to a highly aggressive phenotype. This differential effect was not affected by the different doubling times of the cells, as apparent by similar ablation induction after a synergistic treatment of nsPEFs and Nocodazole. The result suggests that nsPEFs could induce preferential ablation effects on highly aggressive and malignant ovarian cancer cells than their benign counterparts. This study provides an experimental basis for the research on killing malignant tumor cells via electrical treatments and may have clinical implications for treating tumors and preventing tumor recurrence after treatment.