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陡脉冲不可逆电穿孔技术对裸鼠异种移植模型的疗效及机制:一项临床前研究。

Efficacy and mechanism of steep pulse irreversible electroporation technology on xenograft model of nude mice: a preclinical study.

机构信息

Department of Lung Cancer Surgery, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.

College of Nursing, Tianjin Medical University, Tianjin, 300070, China.

出版信息

World J Surg Oncol. 2018 Apr 25;16(1):84. doi: 10.1186/s12957-018-1386-6.

Abstract

BACKGROUND

Steep pulse therapy can irreversible electrically brackdown of tumor membrance and cause cell death. In previous studies, we investigated the effect of steep pulsed electroporation on the killing of large cell lung cancer cell line L981- in vitro, and determined the best parameters for killing lung cancer cells by steep pulse technology. But the optimal parameters and the mechanisms of steep pulse irreversible electroporation technology on nude mouse tumor model are unclear.

METHODS

Three settings of steep pulse therapy parameters were applied to the nude mouse model. An in vivo imaging system was employed to observe the effect of different parameters on the mouse model. The pathological changes of the tumor tissue and immunofluorescence data on Caspase-3 protein expression were recorded.

RESULTS

Under the in vivo imaging system, the steep pulse had an obvious inhibitory effect on the transplanted tumor in the nude mouse model. Pathological tests showed that occurrence of necrosis and apoptosis and expression of Caspase-3 protein in the tumor tissue were increased compared to those in the normal tissue.

CONCLUSIONS

Steep pulse irreversible electroporation technology showed a promising antitumor effect in the nude mouse tumor model. With splint-type electrode, the best treatment parameters determined for the nude mouse tumor model were voltage amplitude 2000 V/cm, pulse width 100 μs, pulse frequency 1 Hz, pulse number 60, and repeat time 3. Moreover, steep pulse induced coagulative necrosis of tumor tissue by cell apoptosis.

摘要

背景

陡脉冲疗法可不可逆地击穿肿瘤膜,导致细胞死亡。在之前的研究中,我们研究了陡脉冲电穿孔对体外大细胞肺癌细胞系 L981 的杀伤作用,并确定了陡脉冲技术杀伤肺癌细胞的最佳参数。但陡脉冲不可逆电穿孔技术对裸鼠肿瘤模型的最佳参数和机制尚不清楚。

方法

应用三种陡脉冲治疗参数设置对裸鼠模型进行处理。采用体内成像系统观察不同参数对小鼠模型的影响。记录肿瘤组织的病理变化和 Caspase-3 蛋白表达的免疫荧光数据。

结果

在体内成像系统下,陡脉冲对裸鼠模型中的移植瘤有明显的抑制作用。病理检查显示,与正常组织相比,肿瘤组织中出现坏死和凋亡,Caspase-3 蛋白表达增加。

结论

陡脉冲不可逆电穿孔技术在裸鼠肿瘤模型中显示出有前途的抗肿瘤效果。使用夹板式电极,确定了裸鼠肿瘤模型的最佳治疗参数为电压幅度 2000 V/cm、脉冲宽度 100 μs、脉冲频率 1 Hz、脉冲数 60、重复时间 3。此外,陡脉冲通过细胞凋亡诱导肿瘤组织凝固性坏死。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27e/5918770/f49f4c863591/12957_2018_1386_Fig1_HTML.jpg

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