Ginsenoside Rh1 regulates the immune microenvironment of hepatocellular carcinoma via the glucocorticoid receptor  

作　　者：Xiong-hui Wang Ya-lan Fu Yan-nan Xu Peng-cheng Zhang Tian-xiao Zheng Chang-quan Ling Ying-lu Feng 

机构地区：[1]Department of Traditional Chinese Medicine,First Affiliated Hospital of Naval Medical University,Shanghai 200433,China [2]PLA Joint Logistics Support Force No.967 Hospital,Dalian 116021,Liaoning Province,China [3]Department of Integrated Traditional Chinese and Western Medicine,Medical College of Qingdao University,Qingdao 266071,Shandong Province,China [4]PLA Joint Logistics Support Force No.920 Hospital,Kunming 650100,Yunnan Province,China [5]First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine),Zhejiang Chinese Medical University,Hangzhou 310053,Zhejiang Province,China [6]Department of Traditional Chinese Medicine,PLA Navy No.971 Hospital,Qingdao 266071,Shandong Province,China

出　　处：《Journal of Integrative Medicine》2024年第6期709-718,共10页结合医学学报（英文版）

基　　金：supported by the Natural Science Foundation of Shandong Province(No.ZR2020MH39)。

摘　　要：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 lenv

关 键 词：Ginsenoside Rh1 Glucocorticoid receptor MHC-I Immune microenvironment Hepatocellular carcinoma 

分 类 号：R285[医药卫生—中药学]