Coskun Alaaddin, Kayhan Handan, Senturk Fatih, Esmekaya Meric Arda, Canseven Ayse Gulnihal
Department of Biophysics, Faculty of Medicine, Gazi University, Ankara, Turkey.
Department of Adult Hematology, Faculty of Medicine, Gazi University, Ankara, Turkey.
Bioelectricity. 2024 Jun 12;6(2):118-125. doi: 10.1089/bioe.2023.0041. eCollection 2024 Jun.
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 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 IC 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.
电化学疗法(ECT)涉及通过电穿孔(EP)局部施加电脉冲以使细胞膜通透性增加。这一过程增强了低渗透性化疗药物的摄取,从而放大了它们的细胞毒性作用。在黑色素瘤治疗中,达卡巴嗪(DTIC)是基石药物,但由于其细胞膜穿透性差而存在局限性,需要使用高剂量,这反过来又导致副作用增加。在我们的研究中,我们使用检测方法研究了DTIC和EP单独及联合使用对黑色素瘤细胞系(SK-MEL-30)以及人皮肤成纤维细胞(HDF)的影响。首先,确定了不同DTIC浓度对SK-MEL-30和HDF细胞活力的影响,结果显示DTIC在较低浓度时对黑色素瘤细胞更有效,而其在1000μM时对两种细胞类型的细胞毒性相似。接下来,1500V/cm的理想电场强度在通透性(84%)和黑色素瘤细胞活力(79%)之间实现了平衡,为有效的ECT铺平了道路。与单独使用DTIC相比,联合应用DTIC-EP(ECT)使SK-MEL-30细胞的IC值降低了2.2倍,使HDF细胞的IC值降低了2.7倍。总之,ECT不仅增加了DTIC对黑色素瘤细胞的细胞毒性,还影响了健康的成纤维细胞。这些发现强调了在黑色素瘤治疗中谨慎、有针对性地管理ECT的必要性。