皮秒脉冲电场抑制肿瘤生长的初步研究  

Preliminary Study of Tumor Growth Inhibition by Picosecond Pulsed Electric Field

作　　者：李成祥[1] 张睿哲[1,2] 姚陈果[1] 米彦[1] 吴丽梅[3] 贾佳[3] 

机构地区：[1]重庆大学输配电装备及系统安全与新技术国家重点实验室,重庆400030 [2]国网北京电力科学研究院,北京100075 [3]重庆医科大学附属第二医院,重庆400010

出　　处：《高电压技术》2016年第8期2501-2507,共7页High Voltage Engineering

基　　金：国家自然科学基金(51307187)~~

摘　　要：皮秒脉冲电场(picosecond pulsed electric field,ps PEF)可以一定程度上抑制Hela细胞生长,然而其能否有效杀伤在体肿瘤组织目前尚不得而知。为此,采用脉宽800 ps,重复频率3 Hz,脉冲个数2 000,50、60、70 k V/cm不同场强的皮秒脉冲电场处理裸鼠皮下宫颈癌组织,通过组织学观察、Western Blotting检测人体抑癌基因P53蛋白表达及抑瘤效应和生存时间观察,初步探讨了ps PEF对在体肿瘤的体内效应。实验结果表明:ps PEF对肿瘤组织有一定杀伤效果,且存在明显剂量依赖正相关关系;P53的表达随皮秒脉冲电场强度的增加逐渐增强,脉冲处理后表达水平最高可以提升74.70%(70 k V/cm),初步推测ps PEF通过上调P53表达促进肿瘤细胞凋亡,从而达到抑制肿瘤生长的目的;ps PEF对在体宫颈癌肿瘤的生长有一定抑制作用,但远期抑制效果不明显。与此同时,ps PEF处理肿瘤组织的过程中,裸鼠生命体征平稳,50 k V/cm组裸鼠无抽搐现象,60 k V/cm、70 k V/cm组裸鼠四肢出现肌肉收缩,初步证实了皮秒脉冲电场的安全性,为实现皮秒脉冲靶向聚焦消融肿瘤奠定了基础。Picosecond pulsed electric field （psPEF） can inhibit the growth of Hela cells to a certain extent by cell expe- riments. However, it is now unclear whether it can effectively kill tumor tissue in vivo. To preliminarily research the effect of psPEF on tumor in vivo, we detected the histological observation, western blotting, inhibition effect, and survival curve observation of cervical tumor on nude mice treated with picosecond pulses（800 ps pulse width, 3 Hz repetition frequency, 2 000 pulses, 50 kV/cm, 60 kV/cm, 70 kV/cm pulsed electric field）. The results show that picosecond pulsed electric field has a certain lethal effect on tumor tissue with a significant dose-response positive relationship. The expression of P53 in- creases gradually with the increasing of the picosecond pulsed electric field. The highest expression levels after pulse processing can be improved to 74.70% （70 kV/cm）. Thus, we initially speculate that picosecond pulsed electric field could promote the tumor cell apoptosis by upregulating the expression of P53, so as to achieve the purpose of inhibiting the growth of tumor tissue. Picosecond pulsed electric field has a certain inhibitory effect on the growth of tumors in vivo, but the long-term suppression effect is not obvious. Meanwhile, nude mice has stable vital signs in the process of picosecond pulsed electric field treatment of tumor tissue. When applying 50 kV/cm picosecond pulsed electric field, nude mice are without the behavior of convulsion. But it appears muscle contraction with the four limbs of nude mice in 60 kV/cm group and 70 kV/cm group. The results initially confirm the safety of picosecond pulsed electric field on animal, and lay a foundation of tumor ablation targeting focused by picosecond pulsed electric field.

关 键 词：皮秒脉冲电场 BALB/C裸鼠 宫颈癌 凋亡 超宽带天线 肌肉收缩 

分 类 号：R73-36[医药卫生—肿瘤]