代谢重编程常常伴随着肝细胞癌（HCC）的进展。破坏的代谢物可作为 HCC 的潜在生物标志物和药物治疗靶点。蝎毒肽提取物 (PESV) 可诱导肿瘤细胞毒性抗增殖作用和细胞凋亡。然而，PESV 的作用机制仍不清楚。本研究旨在探讨荷瘤小鼠模型的血清代谢特征。我们通过将 H22 细胞植入雄性 C57BL/6 小鼠的左肝叶中，生成了原位 HCC 异种移植小鼠模型。手术后，将小鼠随机分为两组：PESV（每天 40 mg/kg PESV 处理，即；n = 6）组和对照组（用溶剂同等处理 14 d，n = 6）组。基于使用超高效液相色谱/四极杆飞行时间质谱的非靶向代谢组学方法，通过单变量和多变量数据分析筛选差异代谢物。血清样品中在负离子模式下共鉴定出 48 种差异代谢物，在正离子模式下共鉴定出 63 种差异代谢物。此外，代谢途径分析表明，氨酰-tRNA生物合成、氨基酸途径、谷胱甘肽代谢、蛋白质转运、蛋白质消化和吸收以及cAMP信号传导途径在PESV诱导的肿瘤抑制中发挥着重要作用。这些发现强调了 PESV 治疗后 HCC 小鼠代谢特征的明显变化，表明已确定的代谢分子作为 HCC 治疗靶点的潜力。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Metabolic reprogramming is frequently accompanied by hepatocellular carcinoma (HCC) progression. Disrupted metabolites act as potential biomarkers and drug therapeutic targets for HCC. Peptide extract of scorpion venom (PESV) induces cytotoxic anti-proliferative effects and apoptosis in tumors. However, the action mechanisms of PESV remain unknown. This study aimed to explore the serum metabolic profiles of tumor-bearing mouse model. We generated an orthotopic HCC xenograft mouse model by implanting H22 cells into the left hepatic lobe of male C57BL/6 mice. After surgery, the mice were assigned to two groups randomly: PESV (PESV-treated 40 mg/kg daily, i.g.; n = 6) and control (treated with the solvent equally for 14 d, n = 6) groups. Based on an untargeted metabolomics approach using ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry, differential metabolites were screened via univariate and multivariate data analyses. A total of 48 differential metabolites in negative ion mode and 63 in positive ion mode were identified in the serum samples. Furthermore, metabolic pathway analysis revealed that aminoacyl-tRNA biosynthesis, amino acid pathway, glutathione metabolism, protein transports, protein digestion and absorption, and cAMP signaling pathways play vital roles in PESV-induced inhibition of tumors. These findings highlight the distinct changes in the metabolic profiles of HCC-bearing mice after PESV treatment, suggesting the potential of the identified metabolic molecules as therapeutic targets for HCC.Copyright © 2024 Elsevier B.V. All rights reserved.