Electroporation of human microvascular endothelial cells: evidence for an anti-vascular mechanism of electrochemotherapy

Recent studies have indicated that the antitumour effectiveness of electroc hemotherapy, a combination of chemotherapeutic drugs with application of hi gh 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 evalu ate the cytotoxicity of electroporation with bleomycin or cisplatin on cult ured human microvascular endothelial cells (HMEC-1). The sensitivity of HME C-1 cells to a 5 min treatment by electroporation with bleomycin or cisplat in (8 electric pulses, pulse duration 100 mus, frequency 1 Hz, electric fie ld intensity 1400 V cm(-1)) was compared to the sensitivity of cells treate d continuously for 3 days with drugs alone. HMEC-1 cells were moderately se nsitive to continuous exposure to cisplatin, but showed greater sensitivity to bleomycin. Combination of a 5 min drug exposure with electric pulses in creased cytotoxicity of cisplatin by -10-fold for cisplatin and -5000-fold for bleomycin. The electroporation of HMEC-1 cells with bleomycin for a 5 m in exposure was -250-fold better than a continuous exposure to the drug alo ne. The results of this study indicate that the anti-tumour action of elect rochemotherapy is likely to be due, in part, to the highly sensitive respon se 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. (C) 2001 Cancer Research Ca mpaign.