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龙葵碱对肝癌Treg细胞介导的肿瘤免疫逃逸的影响 被引量:10

Impacts of solanine on tumor immune escape mediated by Treg cells in hepatocellular carcinoma
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摘要 目的研究龙葵碱对荷肝癌小鼠体内调节性T细胞(Treg细胞)介导肝癌细胞免疫逃逸的影响及其作用机制。方法建立肝癌H22细胞移植瘤小鼠模型,并设对照组、龙葵碱组、TGF-β1抑制剂组和龙葵碱联合TGF-β1抑制剂组。14 d处理称取各组小鼠移植瘤质量,ELISA法检测各组小鼠外周血中IL-2、IL-10、TGF-β1等免疫性抑制细胞因子的含量变化,流式细胞术检测各组小鼠脾淋巴细胞培养液中CD4^(+)、CD4^(+)CD25^(+)Foxp3^(+)Treg的表达水平,免疫荧光法检测小鼠脾淋巴细胞培养液中Foxp3^(+)免疫荧光强度。结果 14 d后,与对照组相比,龙葵碱组、TGF-β1抑制剂组和联合组的肝癌荷瘤小鼠肿瘤瘤重量均显著低于对照组,差异有统计学意义(P<0.05);龙葵碱组、TGF-β1抑制剂组、联合组3组小鼠外周血中免疫性抑制细胞因子IL-2、IL-10、TGF-β1均有明显降低(P<0.05);龙葵碱组、TGF-β1抑制剂组、联合组三组CD4^(+)表达水平均高于对照组,CD4^(+)CD25^(+)Treg的比例则明显下降(P<0.05);免疫荧光染色结果显示,龙葵碱组、TGF-β1抑制剂组、联合组3组荷瘤小鼠Treg细胞中Foxp3^(+)的表达明显低于对照组,差异有统计学意义(P<0.05)。结论龙葵碱可能通过降低荷瘤小鼠Treg细胞含量来改善免疫逃逸,从而发挥抗肿瘤作用。 Objective To research the impacts of solanine on hepatoma cells immune escape mediated by regulatory T cells(Treg cells)in hepatocarcinoma bearing mice and its action mechanism.Methods The mice model of H22 cell transplantation tumor was established and they were divided into the control group,the solanine group,the transforming growth factor-β1(TGF-β1)inhibitor group and the solanine combined with TGF-β1 inhibitor group.After 14 days of treatment,the weight of transplanted tumor in each group was measured,and the level changes of immune inhibitory cytokines such as IL-2,IL-10 and TGF-β1 in the peripheral blood of mice in each group were detected by the enzyme linked immunosorbent assay(ELISA)method.The expression levels of CD4+,CD4+CD25+Foxp3+Treg in spleen lymphocyte culture medium of mice in each group were detected by the flow cytometry method,and the immunofluorescence intensity of Foxp3+in spleen lymphocyte culture medium of mice was de-tected by the immunofluorescence method.Results After 14 days,compared with the control group,the tumor weights of the hepatocarcinoma bearing mice in the solanine group,the TGF-β1 inhibitor group and the com-bined group were all significantly lower than that in the control group,with statistically significant differences(P<0.05).The levels of immunosuppressive cytokines such as IL-2,IL-10 and TGF-β1 in the peripheral blood of mice in the solanine group,the TGF-β1 inhibitor group and the combined group were all significantly decreased(P<0.05).The expression levels of CD4+in the solanine group,the TGF-β1 inhibitor group and the combined group were higher than those in the control group,while the proportion of CD4+CD25+Treg decreased significantly(P<0.05).Immunofluorescence staining showed that the expressions of Foxp3+in Treg cells of hepatocarcinoma bearing mice in the solanine group,the TGF-β1 inhibitor group and the combined group were significantly lower than those in the control group(P<0.05).Conclusion Solanine may play an anti-tumor role by reducing the con-te
作者 高聚伟 徐凯 冉冉 应吟吟 GAO Juwei;XU Kai;RAN Ran;YING Yinyin(Department of Oncology,The Third Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310012,China)
出处 《中国现代医生》 2021年第18期35-38,42,F0003,共6页 China Modern Doctor
基金 浙江省医药卫生科技计划项目(2017KY519)。
关键词 龙葵碱 肝癌 免疫逃逸 TREG细胞 Solanine Hepatocellular carcinoma Immune escape Treg cells
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