Effect of bufalin on lactate dehydrogenase A and regulatory T cells in the tumor microenvironment of hepatocellular carcinoma in mice
10.12007/j.issn.0258-4646.2025.10.003
- VernacularTitle:蟾毒灵对肝细胞癌小鼠肿瘤微环境中乳酸脱氢酶A和调节性T细胞的影响
- Author:
Fangjing YU
1
;
Xinyu FU
;
Bin ZHANG
;
Yan DONG
;
Yujun LI
;
Xiaonan CUI
Author Information
1. 大连医科大学 附属第一医院肿瘤科,辽宁大连 116011;大连医科大学 第一临床学院,辽宁大连 116011;大连医科大学 附属第一医院中西医结合实验室,辽宁大连 116011
- Publication Type:Journal Article
- Keywords:
hepatocellular carcinoma;
bufalin;
regulatory T cell;
lactate dehydrogenase A
- From:
Journal of China Medical University
2025;54(10):876-882
- CountryChina
- Language:Chinese
-
Abstract:
Objective To detect the expression of lactate dehydrogenase A(LDHA),FoxP3,and CD4 in hepatocellular carcinoma(HCC)and to analyze the effect of bufalin on LDHA as well as on the differentiation and function of regulatory T(Treg)cells in the tumor microenvironment of HCC mice.Methods Immunohistochemical staining was performed to detect the difference in the expression of LDHA,FoxP3(Treg cell marker),and CD4 between the tumor and adjacent tissues from 91 HCC patients.Hepl-6 subcutaneous tumor-bearing mouse model was established.The mice were randomly divided into control,bufalin+pyruvic acid,oxalate,and bufalin groups(n=5 each group).The mass and volume of subcutaneous tumors were compared.Immunohistochemical staining was performed to detect the expression of LDHA,FoxP3,and CD4 in tumors of mice in each group.ELISA was used to detect the levels of transforming growth factor β(TGF-β)and interleukin-10(IL-10)in the serum of mice in each group to evaluate the immune function of Treg cells.Results Compared with adjacent tissues,HCC tissues exhibited significantly higher LDHA and FoxP3 expression and lower CD4 expression(P＜0.001).The results of the correlation analysis showed that LDHA was positively correlated with FoxP3 expression and negatively correlated with CD4 expression(P＜0.05).The experimental results of Hep1-6 subcutaneous tumor-bearing mice showed that the tumor volume was significantly smaller in the bufalin and oxalate groups than in the control group and was significantly larger in the bufalin+pyruvic acid group than in the bufalin group(P＜0.001).The results of immunohistochemical staining showed that the expression levels of LDHA and the percentage of FoxP3+cells in the bufalin and oxalate groups were significantly lower than those in the control group,and the percentage of CD4+cells in the bufalin group was significantly higher than that in the control group(P＜0.001).The expres-sion level of LDHA and the percentage of FoxP3+cells in the bufalin+pyruvic acid group were significantly higher than those in the bufalin group,while the percentage of CD4+cells was significantly lower than that in the bufalin group(P＜0.001).The results of ELISA showed that the levels of TGF-β and IL-10 in the bufalin and oxalate groups were significantly lower than those in the control group(P＜0.001).Conclusion Bufalin inhibits cell growth,downregulates LDHA expression,and suppresses the differentiation and proliferation of Treg cells in HCC mice.
