Abstract

Electrochemotherapy (ECT) involves locally applying electrical pulses to permeabilize cell membranes, using electroporation (EP). This process enhances the uptake of low-permeant chemotherapeutic agents, consequently amplifying their cytotoxic effects. In melanoma treatment, dacarbazine (DTIC) is a cornerstone, but it faces limitations because of poor cell membrane penetration, necessitating the use of high doses, which, in turn, leads to increased side effects. In our study, we investigated the effects of DTIC and EP, both individually and in combination, on the melanoma cell line (SK-MEL-30) as well as human dermal fibroblasts (HDF) using in vitro assays. First, the effects of different DTIC concentrations on the viability of SK-MEL-30 and HDF cells were determined, revealing that DTIC was more effective against melanoma cells at lower concentrations, whereas its cytotoxicity at 1000 μM was similar in both cell types. Next, an ideal electric field strength of 1500 V/cm achieved a balance between permeability (84%) and melanoma cell viability (79%), paving the way for effective ECT. The combined DTIC-EP (ECT) application reduced IC50 values by 2.2-fold in SK-MEL-30 cells and 2.7-fold in HDF cells compared with DTIC alone. In conclusion, ECT not only increased DTIC's cytotoxicity against melanoma cells but also affected healthy fibroblasts. These findings emphasize the need for cautious, targeted ECT management in melanoma therapy.

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