Simulation and Experimental Study on Preferential Killing of Chemoresistance Tumor Cells Induced by the High-Frequency Permeation Effect of Nanosecond Pulse Field
Liu Hongmei, Dong Shoulong, Ning Junyi, Zheng Shuang, Yao Chenguo
State Key Laboratory of Power Transmission Equipment & System Security and New Technology Chongqing University Chongqing 400044 China
Abstract:In order to overcome the barrier of clinical tumor treatment—chemoresistance, and to make up for the blank of bioelectric effect on chemoresistance tumor cells (CRTCs) induced by nanosecond pulse electric fields (nsPEFs), simulations and experiments were combined in this paper. Firstly, based on the finite element platform, a five-layer dielectric model considering organelles and a numerical model considering the electroporation of inner and outer membranes were established. The high-frequency permeation effect, targeting characteristics and the influence from cell nucleus size were analyzed. Then, taking A549 and homologous A549/R as research objects, this paper further studied the fluorescence dissipation of inner/outer membrane under nsPEFs, and compared the differences of the morphology and killing effects between A549 and A549/R based on the fluorescent probe and flow techniques. It is shown that nsPEFs can efficiently target the inner membrane and induce the fluorescence dissipation of the cell nuclear membrane. This intracellular effect is positively correlated with the nucleus size (or nucleo-cytoplasmic ratio, NCR), causing higher killing effect on A549/R with higher NCR. Therefore, high voltage nsPEFs can target inner membrane to priority kill CRTCs. These results provide theoretical and experimental basis for selective killing of the CRTCs, and also lay a foundation for nsPEFs as a new physical selective method, which can be combined with other tumor treatment methods to achieve effective ablation of refractory tumor tissues.
刘红梅, 董守龙, 宁郡怡, 郑爽, 姚陈果. 纳秒脉冲高频透膜效应优先杀伤化疗抗性肿瘤细胞的仿真与实验研究[J]. 电工技术学报, 2019, 34(22): 4839-4848.
Liu Hongmei, Dong Shoulong, Ning Junyi, Zheng Shuang, Yao Chenguo. Simulation and Experimental Study on Preferential Killing of Chemoresistance Tumor Cells Induced by the High-Frequency Permeation Effect of Nanosecond Pulse Field. Transactions of China Electrotechnical Society, 2019, 34(22): 4839-4848.
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