Parameter-Dependent Electroporation and Cellular Responses Induced by Microsecond Pulsed Electric Fields: Different...

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive, treatment-resistant tumor requiring novel therapeutic approaches. Electroporation (EP)-based strategies are promising tools for local tumor control and enhanced drug delivery. However, cellular responses and protocols optimization remain poorly investigated in PDAC. Here, we investigated the effects of variable microsecond pulsed electric fields (PEFs) on PANC-1 and MIA PaCa-2 PDAC cells. Immediate responses were assessed via membrane permeabilization and cell death. Delayed effects were evaluated through viability, growth, cell cycle and expression of stress markers. Immediate cell death occurred above specific thresholds in PANC-1 and MIA PaCa-2 cells (16 pulses at 1 kV/cm and 30 pulses at 2.5 kV/cm, respectively), suggesting differential sensitivity to PEFs. Delayed analyses confirmed differences in both viability (-19.3% vs. -46.4% with 4 pulses, 1 kV/cm, 48 h) and growth (-30.3% vs. -57.6% with 4 pulses, 1 kV/cm, 48 h). An opposite modulation of the S-phase population was also observed at 48 h (+7.4% with 20 pulses at 1 kV/cm and -9.2% with 8 pulses at 1 kV/cm for PANC-1 and MIA PaCa-2, respectively). Both cell lines showed similar regulations of apoptosis-associated and autophagy-related markers. Overall, PEFs elicited parameter- and cell-specific responses, supporting fine-tuned EP protocols for pancreatic cancer therapy.