Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Aachen, Germany.
Philips Research, Eindhoven, The Netherlands.
Cardiovasc Intervent Radiol. 2024 Oct;47(10):1384-1391. doi: 10.1007/s00270-024-03847-1. Epub 2024 Sep 3.
Electrochemotherapy, clinically established for treating (sub)cutaneous tumors, has been standardized in the framework of the European Standard Operating Procedure on Electrochemotherapy (ESOPE). Due to common side effects of chemotherapeutic drugs, recent advances focus on non-cytotoxic agents, like calcium, to induce cell death (calcium electroporation). Therefore, this study aims to determine the efficacy of electrochemotherapy with bleomycin or cisplatin, or calcium electroporation on human hepatocellular carcinoma cells (HepG2) in vitro using the ESOPE protocol.
HepG2 cell viability was measured with a MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay after electrochemotherapy with the chemotherapeutic drugs bleomycin or cisplatin (0-20 µM), or after calcium electroporation (0-20 mM), to determine its efficacy on HepG2 cells in vitro using the ESOPE protocol (8 rectangular pulses, 1000 V/cm, 100 µs) compared to non-electroporated drug treatment.
Cell viability was significantly lower in electroporated samples, compared to their non-electroporated controls (27-75% difference). Electrochemotherapy with bleomycin and calcium electroporation, reached (almost) complete cell death (- 1 ± 3% and 2.5 ± 2%), in the lowest concentration of 2.5 µM and 2.5 mM, respectively. Electrochemotherapy with 2.5 µM cisplatin, significantly decreased cell viability to only 68% (± 7%).
Electrochemotherapy with bleomycin or cisplatin, or calcium electroporation were more effective in reducing the HepG2 cell viability in vitro using the ESOPE protocol compared to the non-electroporated drug treatments alone. When comparing electrochemotherapy, HepG2 cells are more sensitive to bleomycin than cisplatin, in similar concentrations. Calcium electroporation has the same effectiveness as electrochemotherapy with bleomycin, but calcium potentially has a better safety profile and several treatment advantages.
电化学疗法已在欧洲电化学疗法标准操作程序（ESOPE）框架内得到临床应用，用于治疗（皮下）肿瘤。由于化疗药物的常见副作用，最近的研究重点是非细胞毒性药物，如钙，以诱导细胞死亡（钙电穿孔）。因此，本研究旨在使用 ESOPE 方案确定电化学疗法联合博来霉素或顺铂或钙电穿孔对人肝癌细胞（HepG2）的疗效。
使用 MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐）测定电化学疗法联合博来霉素或顺铂（0-20µM）或钙电穿孔（0-20mM）后 HepG2 细胞活力，以确定其在 ESOPE 方案（8 个矩形脉冲，1000V/cm，100µs）下对 HepG2 细胞的体外疗效，与未经电穿孔的药物处理相比。
与未经电穿孔的对照相比，电穿孔样品中的细胞活力明显降低（27-75%差异）。博来霉素电化学疗法和钙电穿孔，在最低浓度 2.5µM 和 2.5mM 时，达到（几乎）完全细胞死亡（-1±3%和 2.5±2%）。电化学疗法联合 2.5µM 顺铂，可使细胞活力显著降低至 68%（±7%）。
与未经电穿孔的药物单独治疗相比，使用 ESOPE 方案，博来霉素或顺铂电化学疗法或钙电穿孔在降低 HepG2 细胞活力方面更有效。当比较电化学疗法时，HepG2 细胞对博来霉素比顺铂更敏感，在相似浓度下。钙电穿孔与博来霉素电化学疗法具有相同的疗效，但钙具有更好的安全性和多种治疗优势。
