人参皂苷Rh1通过糖皮质激素受体调节肝细胞癌的免疫微环境

IF 4.2 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE
Journal of Integrative Medicine-Jim Pub Date : 2024-11-01 Epub Date: 2024-09-30 DOI:10.1016/j.joim.2024.09.004
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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引用次数: 0

摘要

研究目的人参皂苷Rh1(G-Rh1)已被证实可抑制乳腺癌和结肠癌的生长,但其对肝细胞癌(HCC)的治疗效果尚不明确。本研究探讨了 G-Rh1 对 HCC 的治疗作用及其机制:方法:采用生物信息学方法分析糖皮质激素受体(GR)的表达以及HCC患者HCC组织中的肿瘤微环境。采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑法在体外研究了 G-Rh1 对 HCC 细胞的影响。在 C57BL/6J 和裸鼠皮下移植模型中,研究了 G-Rh1 的体内治疗效果。此外,还利用流式细胞术分析了肿瘤中浸润免疫细胞的比例,利用Western印迹分析了G-Rh1处理后HCC细胞的GR和主要组织相容性复合体Ⅰ类(MHC-Ⅰ)表达,并将G-Rh1处理后的Hepa1-6细胞与骨髓树突状细胞和B3Z T细胞共培养,进一步分析了G-Rh1诱导树突状细胞(DC)成熟和CD8+ T细胞活化的能力。结果HCC组织中GR表达上调,GR高表达与免疫微环境恶化有关。体外研究表明,G-Rh1 对 HCC 细胞的增殖无明显影响;体内研究表明,G-Rh1 对 C57BL/6J 小鼠有抗肿瘤作用,但对裸鼠无作用。进一步的研究发现,G-Rh1能改善免疫抑制性肿瘤微环境,从而通过增加CD8+ T细胞、成熟DC和MHC-I阳性细胞的浸润来增强来伐替尼的抗肿瘤作用。G-Rh1通过GR抑制作用上调了MHC-I。此外,GR的过表达可消除G-Rh1介导的对Huh7细胞中MHC-I表达的促进作用,以及对DCs成熟和CD8+ T细胞活化的促进作用:结论:G-Rh1可通过靶向GR调节HCC的免疫微环境,从而增强来伐替尼的抗肿瘤作用。本文引用如前Wang XH, Fu YL, Xu YN, Zhang PC, Zheng TX, Ling CQ, Feng YL.人参皂苷Rh1通过糖皮质激素受体调节肝细胞癌的免疫微环境J Integr Med.2024; Epub ahead of print.
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Ginsenoside Rh1 regulates the immune microenvironment of hepatocellular carcinoma via the glucocorticoid receptor.

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.

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来源期刊
Journal of Integrative Medicine-Jim
Journal of Integrative Medicine-Jim Medicine-Complementary and Alternative Medicine
CiteScore
9.20
自引率
4.20%
发文量
3319
期刊介绍: The predecessor of JIM is the Journal of Chinese Integrative Medicine (Zhong Xi Yi Jie He Xue Bao). With this new, English-language publication, we are committed to make JIM an international platform for publishing high-quality papers on complementary and alternative medicine (CAM) and an open forum in which the different professions and international scholarly communities can exchange views, share research and their clinical experience, discuss CAM education, and confer about issues and problems in our various disciplines and in CAM as a whole in order to promote integrative medicine. JIM is indexed/abstracted in: MEDLINE/PubMed, ScienceDirect, Emerging Sources Citation Index (ESCI), Scopus, Embase, Chemical Abstracts (CA), CAB Abstracts, EBSCO, WPRIM, JST China, Chinese Science Citation Database (CSCD), and China National Knowledge Infrastructure (CNKI). JIM Editorial Office uses ThomsonReuters ScholarOne Manuscripts as submitting and review system (submission link: http://mc03.manuscriptcentral.com/jcim-en). JIM is published bimonthly. Manuscripts submitted to JIM should be written in English. Article types include but are not limited to randomized controlled and pragmatic trials, translational and patient-centered effectiveness outcome studies, case series and reports, clinical trial protocols, preclinical and basic science studies, systematic reviews and meta-analyses, papers on methodology and CAM history or education, conference proceedings, editorials, commentaries, short communications, book reviews, and letters to the editor. Our purpose is to publish a prestigious international journal for studies in integrative medicine. To achieve this aim, we seek to publish high-quality papers on any aspects of integrative medicine, such as acupuncture and traditional Chinese medicine, Ayurveda medicine, herbal medicine, homeopathy, nutrition, chiropractic, mind-body medicine, taichi, qigong, meditation, and any other modalities of CAM; our commitment to international scope ensures that research and progress from all regions of the world are widely covered. These ensure that articles published in JIM have the maximum exposure to the international scholarly community. JIM can help its authors let their papers reach the widest possible range of readers, and let all those who share an interest in their research field be concerned with their study.
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