Difference in Membrane Repair Capacity Between Cancer Cell Lines and a Normal Cell Line.
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.
Center for Experimental Drug and Gene Electrotransfer, Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
Stine Krog
SK
Frandsen
Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA, USA.
Anna K
AK
McNeil
Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Ivana
I
Novak
Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA, USA.
Paul L
PL
McNeil
Center for Experimental Drug and Gene Electrotransfer, Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark. karen.julie.gehl@regionh.dk.
Julie
0000-0003-3829-0210
J
Gehl
D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000502:physiology*; D002463:Cell Membrane Permeability; D002470:Cell Survival; D053672:Electrochemotherapy; D018274:Electroporation; D006801:Humans; D008545:Melanoma / Q000473:pathology / Q000628:therapy; D012038:Regeneration
Cancer; Electroporation; In vitro; Membrane repair; Normal