Julita Kulbacka1, Nina Rembiałkowska1, Anna Szewczyk1,2, Helena Moreira3, Anna Szyjka3, Irutė Girkontaitė4, Kamil P Grela5, Vitalij Novickij6. 1. Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, 50-367 Wroclaw, Poland. 2. Department of Animal Developmental Biology, Institute of Experimental Biology, University of Wroclaw, 50-137 Wroclaw, Poland. 3. Department of Basic Medical Science, Faculty of Pharmacy, Wroclaw Medical University, 50-367 Wroclaw, Poland. 4. Department of Immunology, State Research Institute Centre for Innovative Medicine, 08406 Vilnius, Lithuania. 5. Department of Drugs Form Technology, Faculty of Pharmacy, Wroclaw Medical University, 50-367 Wroclaw, Poland. 6. Institute of High Magnetic Fields, Vilnius Gediminas Technical University, 10223 Vilnius, Lithuania.
Abstract
(1) Background: Calcium electroporation (CaEP) is based on the application of electrical pulses to permeabilize cells (electroporation) and allow cytotoxic doses of calcium to enter the cell. (2) Methods: In this work, we have used doxorubicin-resistant (DX) and non-resistant models of human breast cancer (MCF-7/DX, MCF-7/WT) and colon cancer cells (LoVo, LoVo/DX), and investigated the susceptibility of the cells to extracellular Ca2+ and electric fields in the 20 ns-900 ns pulse duration range. (3) Results: We have observed that colon cancer cells were less susceptible to PEF than breast cancer cells. An extracellular Ca2+ (2 mM) with PEF was more disruptive for DX-resistant cells. The expression of glycoprotein P (MDR1, P-gp) as a drug resistance marker was detected by the immunofluorescent (CLSM) method and rhodamine-123 efflux as an MDR1 activity. MDR1 expression was not significantly modified by nanosecond electroporation in multidrug-resistant cells, but a combination with calcium ions significantly inhibited MDR1 activity and cell viability. (4) Conclusions: We believe that PEF with calcium ions can reduce drug resistance by inhibiting drug efflux activity. This phenomenon of MDR mechanism disruption seems promising in anticancer protocols.
(1) Background: Calcium electroporation (CaEP) is based on the application of electrical pulses to permeabilize cells (electroporation) and allow cytotoxic doses of calcium to enter the cell. (2) Methods: In this work, we have used doxorubicin-resistant (DX) and non-resistant models of human breast cancer (MCF-7/DX, MCF-7/WT) and colon cancer cells (LoVo, LoVo/DX), and investigated the susceptibility of the cells to extracellular Ca2+ and electric fields in the 20 ns-900 ns pulse duration range. (3) Results: We have observed that colon cancer cells were less susceptible to PEF than breast cancer cells. An extracellular Ca2+ (2 mM) with PEF was more disruptive for DX-resistant cells. The expression of glycoprotein P (MDR1, P-gp) as a drug resistance marker was detected by the immunofluorescent (CLSM) method and rhodamine-123 efflux as an MDR1 activity. MDR1 expression was not significantly modified by nanosecond electroporation in multidrug-resistant cells, but a combination with calcium ions significantly inhibited MDR1 activity and cell viability. (4) Conclusions: We believe that PEF with calcium ions can reduce drug resistance by inhibiting drug efflux activity. This phenomenon of MDR mechanism disruption seems promising in anticancer protocols.
Entities:
Keywords:
calcium ions; electroporation drug resistance; human adenocarcinoma; membrane permeabilization