Doxorubicin delivery enhanced by electroporation to gastrointestinal adenocarcinoma cells with P-gp overexpression.
Electroporation (EP) can effectively support the penetration of macromolecules from the extracellular space into cells. Electropores induced by the influence of electromagnetic field generate additional paths of transport for macromolecules. The aim of this study was evaluation of the electroporation effect on doxorubicin transport efficiency to human colon (LoVo and LoVo/DX) and gastric (EPG85-257/P and EPG85-257/RDB) adenocarcinoma cells with overexpression of P-glycoprotein and murine macrophage cell line (P388/D1). In our EP experiments cells were placed into a cuvette with aluminum electrodes and pulsed with five square electric pulses of 1300 V/cm and duration of 50 μs each. Cells were also treated with low doxorubicin concentration ([DOX]=1.7 μM). The ultrastructure (TEM) and changes of P-glycoprotein expression of tumor cells subjected to electric field were monitored. The mitochondrial cell function and trypan blue staining were evaluated after 24h. Our results indicate the most pronounced effect of EP with DOX and disturbed ultrastructure in resistant gastric and colon cells with decrease of P-gp expression. Electroporation may be an attractive delivery method of cytostatic drugs in chemotherapy, enabling reduction of drug dose, exposure time and side effects.
Department of Medical Biochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-367 Wroclaw, Poland.
Julita
J
Kulbacka
Department of Animal Developmental Biology, Institute of Experimental Biology, University of Wroclaw, Sienkiewicza 21, 50-335 Wroclaw, Poland.
Małgorzata
M
Daczewska
Department of Animal Developmental Biology, Institute of Experimental Biology, University of Wroclaw, Sienkiewicza 21, 50-335 Wroclaw, Poland.
Magda
M
Dubińska-Magiera
Department of Medical Biochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-367 Wroclaw, Poland.
Anna
A
Choromańska
Department of Medical Biochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-367 Wroclaw, Poland.
Nina
N
Rembiałkowska
Department of Histology and Embryology, University School of Medicine, Chalubinskiego 6a, 50-356 Wroclaw, Poland.
Paweł
P
Surowiak
Polish-Japanese Institute of Information Technology, Koszykowa 86, 02-008 Warsaw, Poland.
Marek
M
Kulbacki
Institute of Biomedical Engineering and Instrumentation, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland.
Małgorzata
M
Kotulska
Department of Medical Biochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-367 Wroclaw, Poland.
Jolanta
J
Saczko
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D004317:Doxorubicin / Q000378:metabolism* / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D018274:Electroporation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D013274:Stomach Neoplasms / Q000473:pathology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004317:Doxorubicin
Adenocarcinoma treatment; Doxorubicin; Electrochemotherapy; Electropermeabilization; Electroporation