| Xu Mingyan,Chen Xian,Zhang Hua,et al.Effects of different doses of X-rays on cGAS-STING signaling pathway and tumor immune microenvironment[J].Chinese Journal of Radiological Medicine and Protection,2024,44(1):1-6 |
| Effects of different doses of X-rays on cGAS-STING signaling pathway and tumor immune microenvironment |
| Received:June 07, 2023 |
| DOI：10.3760/cma.j.cn112271-20230607-00183 |
| KeyWords:Hepatocellular carcinoma Radiotherapy Tumor immune micro environment Macrophages |
| FundProject:新疆维吾尔自治区科技厅天山青年计划(2020Q037) |
| Author Name | Affiliation | E-mail | | Xu Mingyan | Department II of Oncology Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China | | | Chen Xian | Department II of Oncology Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China | | | Zhang Hua | Department II of Oncology Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China | | | Yiliyaer·Nuerrula | Department II of Oncology Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China | | | Xiao Lei | Department II of Oncology Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China | xiaolei_0608@sina.com |
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| Abstract:: |
| Objective To study the effects of different doses of X-ray irradiation on the immune microenvironment and cGAS-STING signaling pathway of hepatocellular carcinoma cells. Methods C57BL/C mice were subcutaneously injected with Hepa 1-6 hepatocellular carcinoma cells in the right axilla to establish a subcutaneous tumor-forming hepatocellular carcinoma model. The mice were randomly divided into 0, 4, 8, 12 Gy irradiation groups, with 10 mice in each group. The body weights and tumor volumes were monitored. Specimens were collected 28 d after irradiation. The ELLSA and Flow Cytometry method was used to compare the macrophage-associated cytokines tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6), chemokine ligand 5 (CCL5), IL-10, IL-13, transforming growth factor-β (TGF-β), IL-4 and macrophage M1, M2 phenotype ratio (M1/M2). Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and immunoblotting assay were used to detect the expression of genes and proteins related to the cGAS-STING signaling pathway in hepatoma cells. Results With the increase of irradiation dose, the tumor volume was significantly reduced (F=8.42, P<0.05), the proportion of cell necrosis increased (F=3.89, P<0.05), the content of macrophage-associated cytokines other than IL-4 increased (F=6.32-15.50, P<0.05), and the proportion of M1 and M2 types of macrophage in the immune microenvironment of hepatocellular carcinoma tumors was elevated (F= 5.46, 5.14, P < 0.05).The gene expression and protein expression levels of cGAS-STING signaling pathway were elevated in hepatocellular carcinoma cells (mRNA expression of cGAS and STING: F=6.35, 16.10, P<0.05; protein expression of cGAS and STING: F=71.31, 37.15, P<0.05). Conclusions X-ray irradiation activates the cGAS-STING signaling pathway in hepatocellular carcinoma cells and contributes to the remodeling of the tumor immune microenvironment. |
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