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

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

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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 inves-tigated 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 immunosup-pressive 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.

Ginsenoside Rh1Glucocorticoid receptorMHC-IImmune microenvironmentHepatocellular carcinoma

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

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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

Department of Integrated Traditional Chinese and Western Medicine,Medical College of Qingdao University,Qingdao 266071,Shandong Province,China

PLA Joint Logistics Support Force No.920 Hospital,Kunming 650100,Yunnan Province,China

First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine),Zhejiang Chinese Medical University,Hangzhou 310053,Zhejiang Province,China

Department of Traditional Chinese Medicine,PLA Navy No.971 Hospital,Qingdao 266071,Shandong Province,China

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2024

10.1016/j.joim.2024.09.004

结合医学学报(英文版)
上海市中西医结合学会,上海长海医院

结合医学学报(英文版)

CSTPCD
影响因子：0.711
ISSN：2095-4964
年,卷(期)：2024.22(6)