肝细胞癌细胞的电化学疗法和钙电穿孔:体外研究。
Electrochemotherapy and Calcium Electroporation on Hepatocellular Carcinoma Cells: An In-Vitro Investigation.
发表日期:2024 Sep 03
作者:
K H K Lindelauf, M Baragona, T Lemainque, R T H Maessen, A Ritter
来源:
Cell Death & Disease
摘要:
临床上用于治疗皮下肿瘤的电化学疗法已在欧洲电化学疗法标准操作程序 (ESOPE) 的框架内实现标准化。由于化疗药物常见的副作用,最近的进展集中在非细胞毒性药物(如钙)上,以诱导细胞死亡(钙电穿孔)。因此,本研究旨在使用 ESOPE 方案确定博莱霉素或顺铂电化学疗法或钙电穿孔对体外人肝细胞癌细胞 (HepG2) 的疗效。使用 MTT 测量 HepG2 细胞活力 (3-(4,5-使用化疗药物博莱霉素或顺铂 (0-20 µM) 进行电化学治疗后,或钙电穿孔 (0-20 mM) 后进行二甲基噻唑-2-基)-2,5-二苯基四唑溴化物测定,以确定其对 HepG2 细胞的功效与非电穿孔药物处理相比,使用 ESOPE 方案(8 个矩形脉冲,1000 V/cm,100 µs)进行体外实验。与非电穿孔对照相比,电穿孔样品中的细胞活力显着较低(差异为 27-75%)。博莱霉素和钙电穿孔电化学疗法在最低浓度分别为 2.5 µM 和 2.5 mM 时,达到(几乎)完全细胞死亡(- 1 ± 3% 和 2.5 ± 2%)。使用 2.5 µM 顺铂进行电化学治疗,细胞活力显着降低至仅 68% (± 7%)。与非电穿孔相比,使用 ESOPE 方案使用博来霉素或顺铂进行电化学治疗或钙电穿孔在体外更有效地降低 HepG2 细胞活力单纯药物治疗。比较电化学疗法时,在相似浓度下,HepG2 细胞对博莱霉素比顺铂更敏感。钙电穿孔与博来霉素电化学疗法具有相同的效果,但钙可能具有更好的安全性和多种治疗优势。© 2024。作者。
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.© 2024. The Author(s).