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纳秒级电脉冲诱导人肝癌细胞发生不可逆电穿孔和凋亡

Irreversible electroporation and apoptosis in human liver cancer cells induced by nanosecond electric pulses.

作者信息

Xiao Deyou, Yao Chenguo, Liu Huan, Li Chengxiang, Cheng Jie, Guo Fei, Tang Liling

机构信息

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.

出版信息

Bioelectromagnetics. 2013 Oct;34(7):512-20. doi: 10.1002/bem.21796. Epub 2013 Jun 6.

Abstract

The goal of this study was to assess the effect of nanosecond electric pulses on HepG2 human liver cancer cells. Electric pulses with a high strength of 10 kV/cm, duration of 500 ns and frequency of 1 Hz were applied to the cells. After delivery of electric pulses, apoptosis, intracellular calcium ion concentrations, transmembrane mitochondrial potentials, electropermeabilization and recovery from electropermeabilization in cells were investigated. The results showed that electric pulse treatment for 20 s and more could trigger apoptosis in cells. Real-time observation indicated an immediate increase in intracellular calcium ion concentration and a dramatic decrease in mitochondrial membrane potential in cells responding to electric pulses. In subsequent experiments, propidium iodide uptake in cells emerged after exposure to electric pulses, indicating electropermeabilization of the cell membrane. Furthermore, recovery from electropermeabilization was not observed even 4 h after the stimulation, demonstrating that irreversible electropermeabilization was induced by electric pulses. In conclusion, electric pulses with a high strength and nanosecond duration can damage cancer cells, accompanied by a series of intracellular changes, providing strong evidence for the application of electric pulses in cancer treatment.

摘要

本研究的目的是评估纳秒级电脉冲对人肝癌HepG2细胞的影响。将强度为10 kV/cm、持续时间为500 ns、频率为1 Hz的电脉冲施加于细胞。施加电脉冲后,对细胞的凋亡、细胞内钙离子浓度、跨膜线粒体电位、电通透化及电通透化恢复情况进行了研究。结果表明,电脉冲处理20 s及以上可引发细胞凋亡。实时观察显示,响应电脉冲的细胞内钙离子浓度立即升高,线粒体膜电位急剧下降。在随后的实验中,细胞暴露于电脉冲后出现碘化丙啶摄取,表明细胞膜发生了电通透化。此外,即使在刺激后4 h也未观察到电通透化的恢复,这表明电脉冲诱导了不可逆的电通透化。总之,高强度和纳秒持续时间的电脉冲可损伤癌细胞,并伴有一系列细胞内变化,为电脉冲在癌症治疗中的应用提供了有力证据。

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