Micro- and Nanosecond Pulses Used in Doxorubicin Electrochemotherapy in Human Breast and Colon Cancer Cells with Drug Resistance

Molecules

Magda Dubińska-Magiera¹  Julia Rudno-Rudzińska²  Jolanta Saczko³  Dagmara Baczyńska³  Nina Rembiałkowska³  Julita Kulbacka³  Vitalij Novickij⁴  Magdalena Maciejewska⁵ 

[1] Department of Animal Developmental Biology, Faculty of Biological Science, University of Wroclaw, Sienkiewicza 21, 50-335 Wroclaw, Poland;Department of General and Oncological Surgery, Medical University Hospital, Borowska 211, 50-556 Wroclaw, Poland;Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland;Institute of High Magnetic Fields, Vilnius Gediminas Technical University, LT-03227 Vilnius, Lithuania;Laboratory of Experimental Anticancer Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Rudolfa Weigla 12, 53-114 Wroclaw, Poland;

关键词: drug resistance;    human adenocarcinoma;    doxorubicin;    electroporation;    drug delivery;   

DOI  :  10.3390/molecules27072052

来源: DOAJ

【 摘 要 】

(1) Background: Pulsed electric field (PEF) techniques are commonly used to support the delivery of various molecules. A PEF seems a promising method for low permeability drugs or when cells demonstrate therapy resistance and the cell membrane becomes an impermeable barrier. (2) Methods: In this study, we have used doxorubicin-resistant and sensitive models of human breast cancer (MCF-7/DX, MCF-7/WT) and colon cancer cells (LoVo, LoVoDX). The study aimed to investigate the susceptibility of the cells to doxorubicin (DOX) and electric fields in the 20–900 ns pulse duration range. The viability assay was utilized to evaluate the PEF protocols’ efficacy. Cell confluency and reduced glutathione were measured after PEF protocols. (3) Results: The obtained results showed that PEFs significantly supported doxorubicin delivery and cytotoxicity after 48 and 72 h. The 60 kV/cm ultrashort pulses × 20 ns × 400 had the most significant cytotoxic anticancer effect. The increase in DOX concentration provokes a decrease in cell viability, affected cell confluency, and reduced GSSH when combined with the ESOPE (European Standard Operating Procedures of Electrochemotherapy) protocol. Additionally, reactive oxygen species after PEF and PEF-DOX were detected. (4) Conclusions: Ultrashort electric pulses with low DOX content or ESOPE with higher DOX content seem the most promising in colon and breast cancer treatment.

【 授权许可】

Unknown