title: Electroporation adopting trains of biphasic pulses enhances in vitro and in vivo the cytotoxic effect of doxorubicin on multidrug resistant colon adenocarcinoma cells (LoVo).
abstract: Few articles in the literature have focused on electroporation as a strategy to reverse multidrug resistance (MDR) of tumour cells and they are mostly limited to the improved efficacy of bleomycin. We tested the application of trains of biphasic pulses to cell suspensions and to murine xenografts as a strategy to increase the uptake of doxorubicin (DOX) and to enhance its cytotoxicity against chemoresistant cells. The human colon adenocarcinoma cell line LoVo DX, expressing MDR phenotype with high levels of P-glycoprotein (P-gp), has been used. The in vitro and in vivo studies gave the following results: (i) the application of the electric pulses to the cell suspension, immediately before DOX administration, induced a significant increase of drug retention; (ii) confocal microscopy observations showed a remarkable increase of intranuclear accumulation of DOX induced by electroporation; (iii) cell survival assay revealed a decrease of cell viability in the cultures treated with the combination of electroporation and doxorubicin; (iv) scanning electron microscopy observations revealed consistent morphological changes after the combined exposure to electroporation and doxorubicin; (v) in implanted mice the combined treatment induced an evident slowdown on the tumour growth when compared to treatment with DOX alone; (vi) histopathological analysis evidenced tumour destruction and its replacement by scar tissue in the tumours treated with the combination of doxorubicin and electroporation.
authors.affiliation: Department of Technology and Health, Italian National Institute of Health, Rome, Italy. stefania.meschini@iss.it
authors.forename: Stefania
authors.initials: S
authors.lastname: Meschini
authors.forename: Maria
authors.initials: M
authors.lastname: Condello
authors.forename: Pasquale
authors.initials: P
authors.lastname: Lista
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Alfonso
authors.initials: A
authors.lastname: Baldi
authors.forename: Gennaro
authors.initials: G
authors.lastname: Citro
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Arancia
authors.forename: Enrico P
authors.initials: EP
authors.lastname: Spugnini
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000378:metabolism; D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage* / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D053672:Electrochemotherapy; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin