title: Electroporation of human microvascular endothelial cells: evidence for an anti-vascular mechanism of electrochemotherapy.
abstract: Recent studies have indicated that the antitumour effectiveness of electrochemotherapy, a combination of chemotherapeutic drugs with application of high voltage electric pulses applied to the tumour nodule (electroporation), result in a significant reduction in tumour blood flow and may therefore be mediated by an anti-vascular mechanism. The aim of this study was to evaluate the cytotoxicity of electroporation with bleomycin or cisplatin on cultured human microvascular endothelial cells (HMEC-1). The sensitivity of HMEC-1 cells to a 5 min treatment by electroporation with bleomycin or cisplatin (8 electric pulses, pulse duration 100 micros, frequency 1 Hz, electric field intensity 1400 V x cm(-1)) was compared to the sensitivity of cells treated continuously for 3 days with drugs alone. HMEC-1 cells were moderately sensitive to continuous exposure to cisplatin, but showed greater sensitivity to bleomycin. Combination of a 5 min drug exposure with electric pulses increased cytotoxicity approximately 10-fold for cisplatin and approximately 5000-fold for bleomycin. The electroporation of HMEC-1 cells with bleomycin for a 5 min exposure was approximately 250-fold better than a continuous exposure to the drug alone. The results of this study indicate that the anti-tumour action of electrochemotherapy is likely to be due, in part, to the highly sensitive response of vascular endothelial cells. Further studies are necessary to identify the determinants of endothelial response and its relationship to the anti-vascular action of electrochemotherapy in vivo.
authors.affiliation: Department of Tumor Biology, Institute of Oncology, Zaloska 2, SI-1000, Ljubljana, Slovenia.
authors.forename: M
authors.initials: M
authors.lastname: Cemazar
authors.forename: C S
authors.initials: CS
authors.lastname: Parkins
authors.forename: A L
authors.initials: AL
authors.lastname: Holder
authors.forename: D J
authors.initials: DJ
authors.lastname: Chaplin
authors.forename: G M
authors.initials: GM
authors.lastname: Tozer
authors.forename: G
authors.initials: G
authors.lastname: Sersa
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001761:Bleomycin / Q000493:pharmacokinetics / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004354:Drug Screening Assays, Antitumor; D004599:Electric Stimulation Therapy; D018274:Electroporation; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy; D010539:Permeability
chemical_list: D000970:Antineoplastic Agents; D001761:Bleomycin; D002945:Cisplatin