Construction of A Mouse Model of Liver Cancer Resistant to PD-1 Monoclonal Antibody and Analysis of Its Metabolic Changes
10.13241/j.cnki.pmb.2025.12.002
- VernacularTitle:耐PD-1单抗的肝癌小鼠模型构建及其代谢组学分析
- Author:
Xin-ru NIU
1
;
Xia WANG
;
Zhi-ting SHU
;
Zi-lan XU
;
Xiao-li QIU
;
Wei DAI
;
Liang-qian ZHANG
;
Xiang-liang DENG
Author Information
1. 广东药科大学中医学院 广东云浮 527322
- Publication Type:Journal Article
- Keywords:
Anti-PD-1 monoclonal antibody;
Drug resistance;
Liver cancer mice;
Metabolomics;
Amino acid metabolism
- From:
Progress in Modern Biomedicine
2025;25(12):1931-1941,1954
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To establish a mouse model of liver cancer resistant to PD-1 monoclonal antibody and analyze the changes in its metabolomics to explore the potential mechanism of drug resistance.Methods:BALB/c mice were randomly divided into control and treatment groups after being loaded with tumor,and a normal group was additionally set up.The normal and control groups were injected with saline,and the treatment group was injected with PD-1 monoclonal antibody,after which the mice in the treatment group were screened for drug resistant and response groups.Observed the drug-resistant situation,body mass,tumor growth and survival rate of mice in each group,calculate the spleen index.The pathological features of tumor tissues were observed by HE staining method.Serum metabolites were detected by non-targeted metabolomics.Finally,a bivariate Pearson correlation analysis was conducted between the differential serum metabolites and tumor size.Results:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established,and the drug resistance rate of the mice was 50％.Compared with the normal and response groups,mice in the resistant group showed an increase in body weight,a significant increase in tumor volume,a decrease in survival rate,and a significant increase in splenic index.There was less lymphocyte infiltration in the tumor tissue.Metabolomics analysis showed that the serum levels of glutamic acid and aspartic acid increased and malic acid decreased in the resistant mice compared with the response group,and these changes were closely related to the arginine biosynthesis pathway.Conclusions:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established.The changes in its peripheral serum metabolomics mainly involve arginine metabolism and the related changes of aspartate,malate and glutamate.
