The Impact of Extracellular Ca(2+) and Nanosecond Electric Pulses on Sensitive and Drug-Resistant Human Breast and Colon Cancer Cells

SIMPLE SUMMARY: The drug resistance phenomenon in cancer constantly induces problems in therapeutic protocols. Pulsed electric fields (PEFs) seem to be a promising method in drug molecule delivery. Here we have proved that electroporation supported by calcium ions can alternate the activity of drug resistance proteins. Our results indicated that MDR1 expression is not significantly modified by nanosecond electroporation in multidrug-resistant cells. However, PEF significantly inhibited MDR1 activity and cell viability when combined with calcium ions. 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 Ca(2+) 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 Ca(2+) (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.