The discriminating effects of nanosecond pulsed electric fields (nsPEFs) between chemoresistant tumor cells (CRTCs) and their respective homologous chemosensitive tumor cells (CSTCs) were investigated based on bioimpedance spectroscopy (BIS). The electrical properties of individual untreated cells were determined by fitting the impedance spectra to an equivalent circuit model and then using aided simulations to calculate the nuclear envelope transmembrane potential (nTMP) and electroporation area on the nuclear envelope. Additionally, fluorescence staining assays of cell monolayers after nanopulse stimulation (80 pulses, 200 ns, 3 kV) were conducted to validate the simulation results. The staining results indicated that CRTCs showed a larger ablation area and lower lethal threshold compared to CSTCs after exposure to the same nsPEF energy, which was in accordance with the higher nTMP and larger electroporation area calculated for CRTCs. The increase in the lethal effects of nsPEFs on CRTCs compared to CSTCs mainly resulted from the superposition of the changes in the electrical properties and nuclear size. The work shows that BIS can distinguish CRTCs and CSTCs and the corresponding nsPEF effects, suggesting potential applications for the optimization of novel anti-chemoresistance methods, including nsPEF-treatments.

基于生物阻抗谱（BIS），研究了耐化学性肿瘤细胞（CRTC）与它们各自的同源化学敏感性肿瘤细胞（CSTC）之间的纳秒脉冲电场（nsPEF）的区分作用。通过将阻抗谱拟合到等效电路模型中，然后使用辅助仿真来计算核包膜跨膜电势（nTMP）和核包膜上的电穿孔面积，可以确定单个未处理细胞的电特性。此外，进行了纳米脉冲刺激（80脉冲，200 ns，3 kV）后细胞单层的荧光染色测定，以验证模拟结果。染色结果表明，在相同的nsPEF能量下，与CSTC相比，CRTC具有更大的消融面积和更低的致死阈值，这与为CRTC计算的较高的nTMP和较大的电穿孔面积相符。与CSTC相比，nsPEF对CRTC的致死作用增加主要是由于电学性质和核尺寸的变化叠加所致。这项工作表明，BIS可以区分CRTC和CSTC以及相应的nsPEF效应，从而为优化包括nsPEF处理在内的新型抗化学耐药方法提供了潜在的应用前景。