Abstract
Electroporation-based treatments and other therapies that permeabilize the plasma membrane have been shown to be more devastating to malignant cells than to normal cells. In this study, we asked if a difference in repair capacity could explain this observed difference in sensitivity. Membrane repair was investigated by disrupting the plasma membrane using laser followed by monitoring fluorescent dye entry over time in seven cancer cell lines, an immortalized cell line, and a normal primary cell line. The kinetics of repair in living cells can be directly recorded using this technique, providing a sensitive index of repair capacity. The normal primary cell line of all tested cell lines exhibited the slowest rate of dye entry after laser disruption and lowest level of dye uptake. Significantly, more rapid dye uptake and a higher total level of dye uptake occurred in six of the seven tested cancer cell lines (p < 0.05) as well as the immortalized cell line (p < 0.001). This difference in sensitivity was also observed when a viability assay was performed one day after plasma membrane permeabilization by electroporation. Viability in the primary normal cell line (98 % viable cells) was higher than in the three tested cancer cell lines (81–88 % viable cells). These data suggest more effective membrane repair in normal, primary cells and supplement previous explanations why electroporation-based therapies and other therapies permeabilizing the plasma membrane are more effective on malignant cells compared to normal cells in cancer treatment.
Highlights
Electroporation-based treatments and other therapies that permeabilize the plasma membrane have been shown to be more devastating to malignant cells than to normal cells
Similar results for calcium electroporation were shown in a 3D in vitro model where normal cell spheroids were much less affected by calcium electroporation than cancer cell spheroids (Frandsen et al 2015)
We aimed to investigate if differences in membrane repair in a number of cancer cell lines, an immortalized cell line, and a normal primary cell line could be part of the explanation for the observed difference in sensitivity between normal and cancer cells for treatments using permeabilization methods
Summary
Electroporation-based treatments and other therapies that permeabilize the plasma membrane have been shown to be more devastating to malignant cells than to normal cells. More rapid dye uptake and a higher total level of dye uptake occurred in six of the seven tested cancer cell lines (p \ 0.05) as well as the immortalized cell line (p \ 0.001) This difference in sensitivity was observed when a viability assay was performed one day after plasma membrane permeabilization by electroporation. Similar results for calcium electroporation were shown in a 3D in vitro model where normal cell spheroids were much less affected by calcium electroporation than cancer cell spheroids (Frandsen et al 2015) It has been shown in vitro that sonoporation, a method where application of low-power ultrasound permeabilizes the cell membrane, causes different effects in normal and malignant cells (Lejbkowicz et al 1993; Lejbkowicz and Salzberg 1997). These empiric observations could help explain the differential sensitivity to electrochemotherapy and calcium electroporation between normal and malignant cells
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