Direct Therapeutic Applications of Calcium Electroporation to Effectively Induce Tumor Necrosis
Direct Therapeutic Applications of Calcium Electroporation to Effectively Induce Tumor Necrosis
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DOI：
10.1158/0008-5472.can-11-3782
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发表时间：
2012-03-15
期刊：
影响因子：
11.2
通讯作者：
Gehl, Julie
中科院分区：
文献类型：
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作者：
Frandsen, Stine Krog;Gissel, Hanne;Gehl, Julie
用短的高电压尖电极电穿孔细胞，引起细胞膜的瞬时透化，允许其他非渗透性离子和分子通过。在这项研究中，我们说明了等渗钙电穿孔如何在体内实现高效的癌细胞杀伤。钙电穿孔引起显着的抗肿瘤反应，其中89%的治疗肿瘤被消除。组织学分析表明肿瘤完全坏死。从机制上讲，钙电穿孔引起急性ATP耗竭可能是由于ATP的细胞使用增加、由于对线粒体的影响而导致的ATP产生减少以及ATP通过透化细胞膜的损失的组合。总之，我们的研究结果提供了一个临床前的概念证明，使用电穿孔加载癌细胞与钙作为一种有效的抗癌治疗。电穿孔设备已经在临床上用于增强对浅表肿瘤的化疗递送，内部肿瘤的试验正在进行中，使得钙电穿孔能够引入临床使用。此外，钙的安全性、可用性和低成本有助于发达国家和发展中国家的许多癌症患者获得这项技术。Cancer Res; 72（6）1336-41. (C)2012年AACR。
Electroporation of cells with short, high-voltage pikes causes a transient permeabilization of cell membranes that permits passage of otherwise nonpermeating ions and molecules. In this study, we illustrate how electroporation with isotonic calcium can achieve highly effective cancer cell kill in vivo. Calcium electroporation elicited dramatic antitumor responses in which 89% of treated tumors were eliminated. Histologic analyses indicated complete tumor necrosis. Mechanistically, calcium electroporation caused acute ATP depletion likely clue to a combination of increased cellular use of ATP, decreased production of ATP due to effects on the mitochondria, as well as loss of ATP through the permeabilized cell membrane. Taken together, our findings offer a preclinical proof of concept for the use of electroporation to load cancer cells with calcium as an efficient anticancer treatment. Electroporation equipment is already used clinically to enhance the delivery of chemotherapy to superficial tumors, with trials on internal tumors in progress, enabling the introduction of calcium electroporation to clinical use. Moreover, the safety profile, availability, and low cost of calcium facilitate access to this technology for many cancer patients in developed and developing countries. Cancer Res; 72(6) 1336-41. (C) 2012 AACR.