异荭草素通过cGAS-STING信号通路介导的免疫反应抑制口腔鳞状细胞癌发展  

Isoorientin inhibits development of oral squamous cell carcinoma through cGAS-STING signaling pathway mediated immune response

作　　者：万兵[1] 张珊 杨文超 杨旭[1] 王新波[1] 梁源[1] WAN Bing;ZHANG Shan;YANG Wenchao;YANG Xu;WANG Xinbo;LIANG Yuan(Department of Stomatology,Luohe Medical College,Luohe 462000,China;Department of Stomatology,Luohe Second People's Hospital,Luohe 462000,China;Department of Stomatology,Luohe Central Hospital,Luohe 462000,China)

机构地区：[1]漯河医学高等专科学校口腔系,漯河462000 [2]漯河市第二人民医院口腔科,漯河462000 [3]漯河市中心医院口腔科,漯河462000

出　　处：《中国免疫学杂志》2025年第4期828-833,共6页Chinese Journal of Immunology

基　　金：漯河医学高等专科学校2022年度科技创新项目(2022KJZD03)。

摘　　要：目的:探究异荭草素(Iso)对口腔鳞状细胞癌(OSCC)发展的影响以及对cGAS-STING信号通路介导的免疫反应的调节作用。方法:将CAL 27细胞分为对照组、Iso低、中、高浓度组、Iso高浓度+cGAS抑制剂组(Iso高+RU.521组)。MTT法检测CAL 27细胞增殖活性;TUNEL法检测CAL 27细胞凋亡情况;Transwell小室实验检测CAL 27细胞迁移和侵袭;Western blot检测CAL 27细胞中cGAS-STING通路相关蛋白的表达;制备小鼠肿瘤移植模型,计算肿瘤抑制率,同时取外周血,流式细胞术检测各组小鼠外周血中T淋巴细胞亚群的分化情况。结果:与对照组相比,Iso处理组细胞的增殖活性、迁移和侵袭细胞数降低,细胞凋亡率、cGAS、STING蛋白及TBK1、IRF3的磷酸化表达、小鼠的肿瘤抑制率及外周血中CD4^(+)T、CD8^(+)T细胞百分数均升高(P<0.05);进一步使用cGAS抑制剂逆转了Iso对OSCC发展的抑制作用以及对cGAS-STING信号通路的促进作用(P<0.05)。结论:Iso可通过激活cGAS-STING信号通路介导的免疫反应抑制OSCC的发展。Objective:To investigate the effect of Isoorientin(Iso)on development of oral squamous cell carcinoma(OSCC)and the regulation on immune response mediated by cGAS-STING signaling pathway.Methods:CAL 27 cells were divided into control group,low,medium and high concentration Iso groups and high concentration Iso+cGAS inhibitor group(high concentration Iso+RU.521 group).Proliferation activity of CAL 27 cells was detected by MTT;TUNEL method was applied to detect apoptosis of CAL 27 cells;Transwell chamber test was applied to detect migration and invasion of CAL 27 cells;Western blot was applied to detect expressions of cGAS-STING pathway related proteins in CAL 27 cells;the tumor transplantation model of mice was prepared,and the tumor inhibition rate was calculated.At the same time,peripheral blood was taken to detect the differentiation of T lymphocyte subsets in peripheral blood of mice in each group by flow cytometry.Results:Compared with control group,proliferation activity,numbers of migration and invasive cells in Iso treated groups were decreased,apoptosis rate,expressions of cGAS,STING protein,and phosphorylation expressions of TBK1,IRF3,tumor inhibition rate of mice,and percentages of CD4^(+)T,CD8^(+)T cells in peripheral blood were increased(P<0.05);further use of cGAS inhibitors reversed the inhibitory effect of Iso on development of OSCC and the promotion on cGAS-STING signaling pathway(P<0.05).Conclusion:Iso can inhibit the development of OSCC by activating the immune response mediated by cGAS-STING signaling pathway.

关 键 词：异荭草素 口腔鳞状细胞癌 cGAS-STING信号通路 免疫反应 

分 类 号：R285.5[医药卫生—中药学]