TAN Qian-ying, XIE Gui-ping, LI Xiang, LIU Lian-fang, WU Guan-nan, WU Xiao-yu, ZHAI Jing. Huangqi Sijunzi Decoction Restrained Gastric Cancer Proliferation via Regulating the Level of PD1 Ubiquitination on T Cells and Remodeling the Tumor Immune Microenvironment[J]. Journal of Nanjing University of traditional Chinese Medicine, 2023, 39(7): 629-636. DOI: 10.14148/j.issn.1672-0482.2023.0629
Citation: TAN Qian-ying, XIE Gui-ping, LI Xiang, LIU Lian-fang, WU Guan-nan, WU Xiao-yu, ZHAI Jing. Huangqi Sijunzi Decoction Restrained Gastric Cancer Proliferation via Regulating the Level of PD1 Ubiquitination on T Cells and Remodeling the Tumor Immune Microenvironment[J]. Journal of Nanjing University of traditional Chinese Medicine, 2023, 39(7): 629-636. DOI: 10.14148/j.issn.1672-0482.2023.0629

Huangqi Sijunzi Decoction Restrained Gastric Cancer Proliferation via Regulating the Level of PD1 Ubiquitination on T Cells and Remodeling the Tumor Immune Microenvironment

  •   OBJECTIVE  To evaluate the effects of Huangqi Sijunzi Decoction on tumor proliferation and immune function of MFC gastric cancer bearing mice.
      METHODS  The MFC gastric cancer subcutaneous tumor model of C57BL/6 mouse was established. 24 C57BL/6 mice were divided into control group, model group, low dose Chinese medicine group (6.24 g· kg-1) and high dose Chinese medicine group (12.48 g· kg-1), with 6 mice in each group. The body weight and tumor volume of these mice were recorded. Expression levels of IFN-γ, TNF-α, IL-2 and IL-8 in peripheral blood of mice in each group were detected by ELISA. The expression levels of CD4+, CD8+, and PD1+ T cell subsets in the tumor, spleen, and thymus of mice were analyzed by flow cytometry. Detect PD1 ubiquitination levels in mouse tumors.
      RESULTS  Compared with control group, the body weight was increased (P < 0.05), the expression of IFN-γ, TNF-α, IL-2 were decreased (P < 0.001), and the expression of IL-8 was increased in model group (P < 0.05). Compared with model group, the tumor volume of mice in high dose Chinese medicine group was remarkable declined (P < 0.05). The expression levels of IFN-γ, IL-2, TNF-α in mouse peripheral blood increased (P < 0.01, P < 0.001), but the expression level of IL-8 decreased (P < 0.05). The expression of CD4+ and CD8+ T cell subsets in tumor, spleen, and thymus of mice was increased in high dose Chinese medicine group (P < 0.001). The PD1+ T cells were decreased (P < 0.001) with the increase of ubiquitination level (P < 0.01).
      CONCLUSION  Huangqi Sijunzi Decoction can upregulate the expression of CD4+and CD8+ T cells in MFC tumor bearing mice, regulate the expression level of cytokines in peripheral blood, and promote the downregulation of PD1 expression by increasing the level of intracellular ubiquitination of T cells, thus inhibiting the proliferation of gastric cancer cells.
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