Ginsenoside Rh1 regulates the immune microenvironment of hepatocellular carcinoma via the glucocorticoid receptor.
10.1016/j.joim.2024.09.004
- Author:
Xiong-Hui WANG
1
;
Ya-Lan FU
2
;
Yan-Nan XU
3
;
Peng-Cheng ZHANG
4
;
Tian-Xiao ZHENG
5
;
Chang-Quan LING
6
;
Ying-Lu FENG
7
,
8
Author Information
1. Department of Traditional Chinese Medicine, First Affiliated Hospital of Naval Medical University, Shanghai 200433, China; PLA Joint Logistics Support Force No. 967 Hospital, Dalian 116021, Liaoning Province, China.
2. Department of Integrated Traditional Chinese and Western Medicine, Medical College of Qingdao University, Qingdao 266071, Shandong Province, China.
3. Department of Traditional Chinese Medicine, First Affiliated Hospital of Naval Medical University, Shanghai 200433, China; PLA Joint Logistics Support Force No. 920 Hospital, Kunming 650100, Yunnan Province, China.
4. First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China.
5. Department of Traditional Chinese Medicine, First Affiliated Hospital of Naval Medical University, Shanghai 200433, China.
6. Department of Traditional Chinese Medicine, First Affiliated Hospital of Naval Medical University, Shanghai 200433, China. Electronic address: changquanling@smmu.edu.cn.
7. Department of Traditional Chinese Medicine, PLA Navy No. 971 Hospital, Qingdao 266071, Shandong Province, China. Electronic address: 18661990776@
8. com.
- Publication Type:Research Support, Non-U.S. Gov't
- Keywords:
Ginsenoside Rh1;
Glucocorticoid receptor;
Hepatocellular carcinoma;
Immune microenvironment;
MHC-I
- MeSH:
Carcinoma, Hepatocellular/genetics*;
Ginsenosides/pharmacology*;
Animals;
Liver Neoplasms/genetics*;
Receptors, Glucocorticoid/genetics*;
Tumor Microenvironment/drug effects*;
Humans;
Mice, Inbred C57BL;
Mice;
Mice, Nude;
Cell Line, Tumor;
Male;
Dendritic Cells/drug effects*
- From:
Journal of Integrative Medicine
2024;22(6):709-718
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:Ginsenoside Rh1 (G-Rh1) has been confirmed to inhibit the growth of breast cancer and colon cancer, but its therapeutic effect on hepatocellular carcinoma (HCC) is unclear. This study investigates the therapeutic effect of G-Rh1 on HCC as well as the underlying mechanism.
METHODS:Bioinformatics methods were used to analyze glucocorticoid receptor (GR) expression and the tumor microenvironment in HCC tissues from HCC patients. The effect of G-Rh1 on HCC cells was investigated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The therapeutic effect of G-Rh1 was investigated in vivo using subcutaneous transplantation models in C57BL/6J and nude mice. Additionally, the proportion of infiltrating immune cells in tumors was analyzed using flow cytometry, the GR and major histocompatibility complex class-I (MHC-I) expression of HCC cells after G-Rh1 treatment was analyzed using Western blotting, and G-Rh1-treated Hepa1-6 cells were cocultured with bone marrow-derived dendritic cells and B3Z T cells to further analyze the ability of G-Rh1 to induce dendritic cell (DC) maturation and CD8+ T cell activation.
RESULTS:GR expression was upregulated in HCC tissues, and high GR expression was associated with a worsened immune microenvironment. In vitro studies showed that G-Rh1 had no significant effect on the proliferation of HCC cells, while in vivo studies showed that G-Rh1 exerted antitumor effects in C57BL/6J mice but not in nude mice. Further research revealed that G-Rh1 ameliorated the immunosuppressive tumor microenvironment, thereby enhancing the antitumor effects of lenvatinib by increasing the infiltration of CD8+ T cells, mature DCs, and MHC-I-positive cells. MHC-I was upregulated by G-Rh1 via GR suppression. Moreover, overexpression of GR abolished the G-Rh1-mediated promotion of MHC-I expression in Huh7 cells, as well as the maturation of DCs and the activation of CD8+ T cells.
CONCLUSION:G-Rh1 can regulate the immune microenvironment of HCC by targeting GR, thus increasing the antitumor effect of lenvatinib. Please cite this article as: Wang XH, Fu YL, Xu YN, Zhang PC, Zheng TX, Ling CQ, Feng YL. Ginsenoside Rh1 regulates the immune microenvironment of hepatocellular carcinoma via the glucocorticoid receptor. J Integr Med. 2024; 22(6): 710-720.
