Abstract
Simple SummaryThe 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.(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.
Highlights
Multidrug resistance (MDR) of cancer cells is a high-priority biomedical problem that is constantly being discussed [1]
The purpose of this study was to investigate the dependence of cell permeabilization on the applied electric field parameters and the alternation on the drug resistance phenomenon in the used cell models after the PEF exposure
The most notable difference was observed between breast and colon cancer cells (Figure 2A,B vs. Figure 2C,D)
Summary
Multidrug resistance (MDR) of cancer cells is a high-priority biomedical problem that is constantly being discussed [1]. The available data indicate that throughout chemotherapeutic clinical procedures, a significant reduction of the cytotoxic effect of a variety of chemotherapeutic agents can be observed, including anthracyclines, vinca alkaloids, and epipodophyllotoxins [2,3]. This phenomenon is called acquired drug resistance and commonly regards breast cancer [4]. The second type of resistance-primary or intrinsic resistance is caused by the primary overexpression of specific proteins and protein pumps that effectively remove drug molecules from the cells [5] In this group, we can include colon and rectal cancer [6]. Cells can acquire resistance to drugs as a consequence of the long-term therapy [12]
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