Nanosecond pulse effectively ablated hepatocellular carcinoma with alterations in the gut microbiome and serum metabolites

Yawen Zou; Ying Sun; Xinhua Chen; Liangjie Hong; Gang Dong; Xiwen Bai; Haiyu Wang; Benchen Rao; Zhigang Ren; Zujiang Yu

doi:10.3389/fphar.2023.1163628

Nanosecond pulse effectively ablated hepatocellular carcinoma with alterations in the gut microbiome and serum metabolites

Front Pharmacol. 2023 May 10:14:1163628. doi: 10.3389/fphar.2023.1163628. eCollection 2023.

Authors

Yawen Zou^{1

2

3}, Ying Sun^{1

2

3}, Xinhua Chen², Liangjie Hong², Gang Dong⁴, Xiwen Bai⁵, Haiyu Wang^{1

2

3}, Benchen Rao^{1

2

3}, Zhigang Ren^{1

2

3}, Zujiang Yu^{1

3}

Affiliations

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

Abstract

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in the world. Nanosecond pulsed electric fields (nsPEFs) have emerged as a new treatment for cancer. This study aims to identify the effectiveness of nsPEFs in the treatment of HCC and analyze the alterations in the gut microbiome and serum metabonomics after ablation. Methods: C57BL/6 mice were randomly divided into three groups: healthy control mice (n = 10), HCC mice (n = 10), and nsPEF-treated HCC mice (n = 23). Hep1-6 cell lines were used to establish the HCC model in situ. Histopathological staining was performed on tumor tissues. The gut microbiome was analyzed by 16S rRNA sequencing. Serum metabolites were analyzed by liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis. Spearman's correlation analysis was carried out to analyze the correlation between the gut microbiome and serum metabonomics. Results: The fluorescence image showed that nsPEFs were significantly effective. Histopathological staining identified nuclear pyknosis and cell necrosis in the nsPEF group. The expression of CD34, PCNA, and VEGF decreased significantly in the nsPEF group. Compared with normal mice, the gut microbiome diversity of HCC mice was increased. Eight genera including Alistipes and Muribaculaceae were enriched in the HCC group. Inversely, these genera decreased in the nsPEF group. LC-MS analysis confirmed that there were significant differences in serum metabolism among the three groups. Correlation analysis showed crucial relationships between the gut microbiome and serum metabolites that are involved in nsPEF ablation of HCC. Conclusion: As a new minimally invasive treatment for tumor ablation, nsPEFs have an excellent ablation effect. The alterations in the gut microbiome and serum metabolites may participate in the prognosis of HCC ablation.

Keywords: ablation; gut microbiome; hepatocellular carcinoma; nanosecond pulsed electric fields; serum metabolites.

Grants and funding

This study was sponsored by grants from the National S&T Major Project of China (2018ZX10301201) and the National Natural Science Foundation of China (82027803, 82070643, and U2004121).