Nanosecond pulsed electric field ablates rabbit VX2 liver tumors in a non-thermal manner

Qing-Gang Li; Zhen-Guo Liu; Gang Dong; Ying Sun; Ya-Wen Zou; Xiao-Long Chen; Bin Wu; Xin-Hua Chen; Zhi-Gang Ren

doi:10.1371/journal.pone.0273754

Nanosecond pulsed electric field ablates rabbit VX2 liver tumors in a non-thermal manner

PLoS One. 2023 Mar 15;18(3):e0273754. doi: 10.1371/journal.pone.0273754. eCollection 2023.

Authors

Qing-Gang Li^{1

2}, Zhen-Guo Liu^{1

2

3}, Gang Dong⁴, Ying Sun^{1

2}, Ya-Wen Zou^{1

2}, Xiao-Long Chen^{1

2}, Bin Wu³, Xin-Hua Chen^{3

5}, Zhi-Gang Ren^{1

2

3}

Affiliations

¹ Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
³ Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou, China.
⁴ Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁵ Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Abstract

Background: Liver tumor remains an important cause of cancer-related death. Nanosecond pulsed electric fields (nsPEFs) are advantageous in the treatment of melanoma and pancreatic cancer, but their therapeutic application on liver tumors need to be further studied.

Methods: Hep3B cells were treated with nsPEFs. The biological behaviors of cells were detected by Cell Counting Kit-8, 5-ethynyl-20-deoxyuridine, and transmission electron microscopy (TEM) assays. In vivo, rabbit VX2 liver tumor models were ablated by ultrasound-guided nsPEFs and radiofrequency ablation (RFA). Contrast-enhanced ultrasound (CEUS) was used to evaluate the ablation effect. HE staining and Masson staining were used to evaluate the tissue morphology after ablation. Immunohistochemistry was performed to determine the expression of Ki67, proliferating cell nuclear antigen, and α-smooth muscle actin at different time points after ablation.

Results: The cell viability of Hep3B cells was continuously lower than that of the control group within 3 days after pulse treatment. The proliferation of Hep3B cells was significantly affected by nsPEFs. TEM showed that Hep3B cells underwent significant morphological changes after pulse treatment. In vivo, CEUS imaging showed that nsPEFs could completely ablate model rabbit VX2 liver tumors. After nsPEFs ablation, the area of tumor fibrosis and the expression of Ki67, proliferating cell nuclear antigen, and α-smooth muscle actin were decreased. However, after RFA, rabbit VX2 liver tumor tissue showed complete necrosis, but the expression of PCNA and α-smooth muscle actin did not decrease compared to the tumor group.

Conclusions: nsPEFs can induce Hep3B cells apoptosis and ablate rabbit VX2 liver tumors in a non-thermal manner versus RFA. The ultrasound contrast agent can monitor immediate effect of nsPEF ablation. This study provides a basis for the clinical study of nsPEFs ablation of liver cancer.

Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins*
Animals
Apoptosis
Ki-67 Antigen
Liver Neoplasms* / diagnostic imaging
Liver Neoplasms* / metabolism
Liver Neoplasms* / therapy
Proliferating Cell Nuclear Antigen
Rabbits

Substances

Proliferating Cell Nuclear Antigen
Actins
Ki-67 Antigen

Grants and funding

This study was supported by grants from the National S&T Major Project of China(2018ZX10301201-008) and the National Natural Science Foundation of China (U2004121, 82027803) to Ren Zhigang. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.