Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska cesta 2, Ljubljana, Slovenia.
University of Ljubljana, Faculty of Medicine, Vrazov Trg 2, Ljubljana, Slovenia.
Sci Rep. 2018 Jun 20;8(1):9412. doi: 10.1038/s41598-018-27728-z.
Calcium electroporation (CaEP) is a novel anti-tumour treatment that induces cell death by internalization of large quantities of calcium. The anti-tumour effectiveness of CaEP has been demonstrated in vitro, in vivo, and in preliminary clinical trials; however, its effects on the vasculature have not been previously investigated. Using a dorsal window chamber tumour model, we observed that CaEP affected to the same degree normal and tumour blood vessels in vivo, as it disrupted the vessels and caused tumour eradication by necrosis. In all cases, the effect was more pronounced in small vessels, similar to electrochemotherapy (ECT) with bleomycin. In vitro studies in four different cell lines (the B16F1 melanoma, HUVEC endothelial, FADU squamous cell carcinoma, and CHO cell lines) confirmed that CaEP causes necrosis associated with acute and severe ATP depletion, a picture different from bleomycin with electroporation. Furthermore, CaEP considerably inhibited cell migratory capabilities of endothelial cells and their potential to form capillary-like structures. The finding that CaEP has anti-vascular effects and inhibits cell migration capabilities may contribute to the explanation of the high efficacy observed in preclinical and clinical studies.
钙电穿孔（CaEP）是一种通过大量内吞钙离子诱导细胞死亡的新型抗肿瘤治疗方法。CaEP 的抗肿瘤效果已在体外、体内和初步临床试验中得到证实；然而，其对血管的影响尚未得到研究。使用背部窗口室肿瘤模型，我们观察到 CaEP 在体内对正常和肿瘤血管的影响程度相同，因为它破坏了血管并通过坏死导致肿瘤消除。在所有情况下，其效果在小血管中更为明显，类似于博来霉素的电化学疗法（ECT）。在四种不同细胞系（B16F1 黑色素瘤、HUVEC 内皮细胞、FADU 鳞状细胞癌和 CHO 细胞系）的体外研究证实，CaEP 导致与急性和严重 ATP 耗竭相关的坏死，与博来霉素联合电穿孔的情况不同。此外，CaEP 极大地抑制了内皮细胞的迁移能力及其形成毛细血管样结构的潜力。CaEP 具有抗血管作用并抑制细胞迁移能力的发现可能有助于解释在临床前和临床研究中观察到的高疗效。
