苦杏仁苷通过JAK2 / STAT3信号通路促进T细胞抑制HBV相关肝癌进

StephenW

Amygdalin promotes the activity of T cells to suppress the progression of HBV-related hepatocellular carcinoma via the JAK2/STAT3 signaling pathway
Ruoyu Wang  1 , Dong Zhang  2 , Kewei Sun  1 , Jianping Peng  1 , Wenfang Zhu  1 , Sihan Yin  1 , Dan Tang  1 , Yunan Wu  3
Affiliations
Affiliations

    1
    Department of Hepatology, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China.
    2
    Department of Hepatology, Guangdong Hospital of Traditional Chinese Medicine in Zhuhai, Zhuhai, 519015, Guangdong, China.
    3
    Department of Hepatology, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China. [email protected].

    PMID: 33435880 DOI: 10.1186/s12879-020-05713-0

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Abstract

Background: Hepatitis B virus (HBV) infection is a high-risk factor of hepatocellular carcinoma (HCC). Cellular immune responses are essential for HCC development, and the CD4+ and CD8+ T subtypes are identified as the primary anti-tumor immune cells. In the study, we investigated the effect and mechanism of amygdalin in the cellular immune response in HBV-related HCC and HCC progression.

Methods: The cell proliferation was examined by MTT analysis. Cells metastasis ability was detected by Invasion and migration assays. Quantification of apoptotic cells was performed with Flow cytometer assay. The protein levels of p-STAT3, STAT3, p-JAK2, JAK2, caspase-3, cleaved caspase-3 were detected by performing immunoblotting assays.

Results: We demonstrate that amygdalin treatment could rescue the HBV-T cell viability and IFN-γ and TNF-αproduction. In HBV-T cells, the MFI levels of CD8+ are lower than that in NC-T cells. Moreover, the phosphorylation levels of STAT3 and JAK2 are higher in HBV-T cells, compared to those in NC-T cells, and then reduced by amygdalin treatment. Co-culture with HBV-T cells could reduce IFN-γ and TNF-α, production while increase IL-6 and IL-10 production in HepG2.2.15 cells; these alterations could be partially reversed by amygdalin pretreatment. Finally, co-culture with HBV-T cells significantly promoted the cell viability, inhibited the apoptosis, and promoted the migration of HepG2.2.15 cells, and these alterations could be partially reversed by amygdalin treatment.

Conclusion: Our findings provide a rationale for further studies on the functions and mechanism of amygdalin inhibiting HBV-related HCC cell proliferation, invasion, and migration via T cell-mediated tumor immunity.

Keywords: Amygdalin; Hepatitis B virus (HBV); Hepatocellular carcinoma (HCC); T cell; The JAK2/STAT3 signaling.

StephenW

苦杏仁苷通过JAK2 / STAT3信号通路促进T细胞抑制HBV相关肝癌进展的活性
王若瑜1，董冬2，孙可伟1，彭建平1，朱文芳1，四汉音1，丹堂1，吴云南3
隶属关系
隶属关系

    1个
    湖南中医药大学附属第一医院肝科，湖南长沙410007
    2
    广东省珠海市广东省中医院肝病科，广东珠海519015。
    3
    湖南中医药大学附属第一医院肝科，湖南长沙410007 [email protected]。

    PMID：33435880 DOI：10.1186 / s12879-020-05713-0

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抽象

背景：乙型肝炎病毒（HBV）感染是肝细胞癌（HCC）的高危因素。细胞免疫反应对于肝癌的发展至关重要，并且CD4 +和CD8 + T亚型被确定为主要的抗肿瘤免疫细胞。在这项研究中，我们研究了苦杏仁苷在HBV相关HCC和HCC进展中细胞免疫应答中的作用和机制。

方法：MTT法检测细胞增殖。通过侵袭和迁移测定法检测细胞的转移能力。用流式细胞仪分析对凋亡细胞进行定量。通过进行免疫印迹测定来检测p-STAT3，STAT3，p-JAK2，JAK2，caspase-3，裂解的caspase-3的蛋白水平。

结果：我们证明苦杏仁苷治疗可以挽救HBV-T细胞的活力以及IFN-γ和TNF-α的产生。在HBV-T细胞中，CD8 +的MFI水平低于NC-T细胞。此外，与NC-T细胞相比，HBV-T细胞中STAT3和JAK2的磷酸化水平更高，然后通过苦杏仁苷处理降低。与HBV-T细胞共培养可降低HepG2.2.15细胞中IFN-γ和TNF-α的产生，同时增加IL-6和IL-10的产生。这些改变可以通过苦杏仁苷预处理而部分逆转。最后，与HBV-T细胞共培养可显着提高细胞活力，抑制细胞凋亡，并促进HepG2.2.15细胞的迁移，而苦杏仁苷处理可部分逆转这些改变。

结论：我们的发现为进一步研究苦杏仁苷通过T细胞介导的肿瘤免疫抑制HBV相关HCC细胞增殖，侵袭和迁移的功能和机理提供了理论依据。

关键词：苦杏仁苷；乙型肝炎病毒（HBV）；肝细胞癌（HCC）； T细胞JAK2 / STAT3信令。

StephenW

https://bmcinfectdis.biomedcentr ... 879-020-05713-0.pdf