Zou Yawen, Sun Ying, Chen Xinhua, Hong Liangjie, Dong Gang, Bai Xiwen, Wang Haiyu, Rao Benchen, Ren Zhigang, Yu Zujiang
Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou, China.
Front Pharmacol. 2023 May 10;14:1163628. doi: 10.3389/fphar.2023.1163628. eCollection 2023.
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. C57BL/6 mice were randomly divided into three groups: healthy control mice ( = 10), HCC mice ( = 10), and nsPEF-treated HCC mice ( = 23). Hep1-6 cell lines were used to establish the HCC model . 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. 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 and 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. 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.
肝细胞癌（HCC）是全球癌症相关死亡的第三大主要原因。纳秒级脉冲电场（nsPEFs）已成为一种新的癌症治疗方法。本研究旨在确定nsPEFs治疗HCC的有效性，并分析消融后肠道微生物群和血清代谢组学的变化。将C57BL/6小鼠随机分为三组：健康对照小鼠（n = 10）、HCC小鼠（n = 10）和nsPEF治疗的HCC小鼠（n = 23）。使用Hep1-6细胞系建立HCC模型。对肿瘤组织进行组织病理学染色。通过16S rRNA测序分析肠道微生物群。通过液相色谱-质谱联用（LC-MS）代谢组学分析血清代谢物。进行Spearman相关性分析以分析肠道微生物群与血清代谢组学之间的相关性。荧光图像显示nsPEFs具有显著疗效。组织病理学染色显示nsPEF组出现核固缩和细胞坏死。nsPEF组中CD34、PCNA和VEGF的表达显著降低。与正常小鼠相比，HCC小鼠的肠道微生物群多样性增加。包括[具体菌属1]和[具体菌属2]在内的8个菌属在HCC组中富集。相反，这些菌属在nsPEF组中减少。LC-MS分析证实三组之间血清代谢存在显著差异。相关性分析表明，肠道微生物群与参与nsPEF消融HCC的血清代谢物之间存在关键关系。作为一种新的肿瘤消融微创治疗方法，nsPEFs具有出色的消融效果。肠道微生物群和血清代谢物的变化可能参与HCC消融的预后。
