Electroporation: new strategy to improve the drug uptake and overcome the tumour resistance
Electrochemotherapy is an innovative therapeutic strategy to overcome multidrug resistance (MDR) phenomenon of several neoplasms. New anticancer treatment combines the administration of a chemotherapeutic agent with the application of electric pulses (electroporation, EP) having appropriate waveforms to increase drug uptake. Its efficacy as adjuvant therapy has been already demonstrated in veterinary patients, in combination with several anticancer agents resulting in enhanced cytotoxicity. The main goal of our project is to increase the effectiveness of doxorubicin (DOX) on MDR human colon adenocarcinoma cell line (LoVo DX) and mitomycin C (MMC) on two human breast adenocarcinoma cell lines (MCF-7 WT and MCF-7 DX), by using trains of biphasic pulses. The in vitro experiments of the combined treatment (EP plus DOX) showed the enhancement of DOX accumulation and nuclear distribution on LoVo DX cell suspension, evaluated by flow cytometry and confocal microscopy, respectively. Moreover, evident morphological changes were observed by scanning electron microscopy. MTT assay showed that MCF-7 cells treated with EP alone showed the same cell viability as the control; this proves that electrical impulses alter only the membrane permeability favouring drug uptake without inducing a cytotoxic effect on tumour cells. Cell viability assay showed a 20% reduction after the combined EP plus MMC treatment. Further studies will be carried out to confirm the cytotoxic damage and assess the role of electrochemotherapy in the pharmacological resistance phenomenon.
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