Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland.
Medical University Hospital, 50-556 Wroclaw, Poland.
Int J Mol Sci. 2021 Oct 18;22(20):11245. doi: 10.3390/ijms222011245.
Electroporation is influenced by the features of the targeted cell membranes, e.g., the cholesterol content and the surface tension of the membrane. The latter is eventually affected by the organization of actin fibers. Atorvastatin is a statin known to influence both the cholesterol content and the organization of actin. This work analyzes the effects of the latter on the efficacy of electroporation of cancer cells. In addition, herein, electroporation was combined with calcium chloride (CaEP) to assess as well the effects of the statin on the efficacy of electrochemotherapy. Cholesterol-rich cell lines MDA-MB231, DU 145, and A375 underwent (1) 48 h preincubation or (2) direct treatment with 50 nM atorvastatin. We studied the impact of the statin on cholesterol and actin fiber organization and analyzed the cells' membrane permeability. The viability of cells subjected to PEF (pulsed electric field) treatments and CaEP with 5 mM CaCl was examined. Finally, to assess the safety of the therapy, we analyzed the N-and E-cadherin localization using confocal laser microscopy. The results of our investigation revealed that depending on the cell line, atorvastatin preincubation decreases the total cholesterol in the steroidogenic cells and induces reorganization of actin nearby the cell membrane. Under low voltage PEFs, actin reorganization is responsible for the increase in the electroporation threshold. However, when subject to high voltage PEF, the lipid composition of the cell membrane becomes the regulatory factor. Namely, preincubation with atorvastatin reduces the cytotoxic effect of low voltage pulses and enhances the cytotoxicity and cellular changes induced by high voltage pulses. The study confirms that the surface tension regulates of membrane permeability under low voltage PEF treatment. Accordingly, to reduce the unfavorable effects of preincubation with atorvastatin, electroporation of steroidogenic cells should be performed at high voltage and combined with a calcium supply.
电穿孔受靶细胞膜特性的影响，例如胆固醇含量和膜的表面张力。后者最终受肌动蛋白纤维的组织影响。阿托伐他汀是一种已知能影响胆固醇含量和肌动蛋白组织的他汀类药物。本工作分析了后者对癌细胞电穿孔效果的影响。此外，本文将电穿孔与氯化钙（CaEP）结合，以评估他汀类药物对电化学疗法效果的影响。富含胆固醇的细胞系 MDA-MB231、DU 145 和 A375 经历了 (1) 48 小时预孵育或 (2) 直接用 50 nM 阿托伐他汀处理。我们研究了他汀类药物对胆固醇和肌动蛋白纤维组织的影响，并分析了细胞的膜通透性。检查了经 PEF（脉冲电场）处理和用 5 mM CaCl 进行 CaEP 处理的细胞的活力。最后，为了评估治疗的安全性，我们使用共聚焦激光显微镜分析了 N-和 E-钙粘蛋白的定位。我们的研究结果表明，根据细胞系的不同，阿托伐他汀预孵育会降低甾体生成细胞中的总胆固醇，并诱导细胞膜附近肌动蛋白的重新排列。在低电压 PEF 下，肌动蛋白的重排是增加电穿孔阈值的原因。然而，当受到高电压 PEF 时，细胞膜的脂质组成成为调节因素。即，阿托伐他汀预孵育会降低低电压脉冲的细胞毒性作用，并增强高电压脉冲诱导的细胞毒性和细胞变化。该研究证实，在低电压 PEF 处理下，表面张力调节细胞膜通透性。因此，为了减少阿托伐他汀预孵育的不利影响，应在高电压下对甾体生成细胞进行电穿孔，并结合钙供应。
Zotero 插件
