首页|金合欢素调节STING/TBK1/IRF3通路介导的免疫反应对宫颈癌细胞恶性进展的影响

金合欢素调节STING/TBK1/IRF3通路介导的免疫反应对宫颈癌细胞恶性进展的影响

Effect of acacetin on the malignant progression of cervical cancer cells by regulating the STING/TBK1/IRF3 pathway mediated immune response

扫码查看
目的 探讨金合欢素(Aca)调节干扰素基因刺激蛋白(STING)/TANK结合激酶1(TBK1)/干扰素调节因子3(IRF3)通路介导的免疫反应对宫颈癌细胞恶性进展的影响.方法 HeLa细胞分为空白组、Aca低浓度组、Aca中浓度组、Aca 高浓度组(Aca-L 组、Aca-M 组、Aca-H 组)、STING 抑制剂(H-151)组、Aca-H+H-151 组,采用 EdU染色和CCK-8、Transwell、划痕实验分别检测细胞增殖、侵袭、迁移;Western blot检测STING、p-TBK1、p-IRF3蛋白.将上述各组HeLa细胞与CD8+T细胞共孵育并依次命名为HeLa+CD8+T组、CD8+T+Aca-L组、CD8+T+Aca-M组、CD8+T+Aca-H组、CD8+T+H-151组、CD8+T+Aca-H+H-151组,检测共培养上清液中穿孔素、γ-干扰素、粒酶B水平及CD8+T细胞对HeLa的杀伤力.结果 与空白组相比,Aca-L组、Aca-M组、Aca-H组HeLa细胞增殖、侵袭及迁移能力降低,STING、p-TBK1、p-IRF3蛋白上调(P<0.05),H-151组对应指标变化趋势与Aca-H组相反(P<0.05).与HeLa+CD8+T 组相比,CD8+T+Aca-L 组、CD8+T+Aca-M 组、CD8+T+Aca-H 组 CD8+T 细胞分泌穿孔素、γ-干扰素、粒酶B水平升高,CD8+T细胞对HeLa细胞杀伤力增强(P<0.05),CD8+T+H-151组对应指标变化趋势与CD8+T+Aca-H组相反(P<0.05);H-151逆转了高浓度Aca对HeLa细胞恶性生物学行为及CD8+T细胞免疫功能的影响.结论 Aca可能通过激活STING/TBK1/IRF3通路抑制HeLa细胞恶性生物学行为,并增强了 CD8+T细胞免疫功能.
Objective To investigate the effect of acacetin on the malignant progression of cervical cancer cells by regulating the immune response mediated by the stimulator of interferon gene(STING)/TANK binding kinase 1(TBK1)/interferon regulatory factor 3(IRF3)pathway.Methods HeLa cells were separated into blank group,low,medium,and high concentration Aca groups(Aca-L group,Aca-M group,Aca-H group),STING inhibitor(H-151)group,and Aca-H+H-151 group.EdU staining and CCK-8,Transwell and scratch assay were used to detect cell proliferation,invasion and migration,respectively.Western blot was applied to detect STING,p-TBK1,and p-IRF3 proteins.The HeLa cells and CD8+T cells in the above groups were co cultured and were sequentially named HeLa+CD8+T group,CD8+T+Aca-L group,CD8+T+Aca-M group,CD8+T+Aca-H group,CD8+T+H-151 group,and CD8+T+Aca-H+H-151 group.Detect levels of per-forin,interferon-γ,and granzyme B in the supernatant of co culture systems and the effect of CD8+T cells on the cytotoxicity of HeLa cells.Results Compared with the blank group,the proliferation,invasion and migration of HeLa cells decreased,the STING,p-TBK1,and p-IRF3 proteins were upregulated in Aca-L,Aca-M and Aca-H groups(P<0.05),the change trend of corresponding indicators in the H-151 group was opposite to that in the Aca-H group(P<0.05).Compared with the HeLa+CD8+T group,the levels of perforin,interferon-γ,and Granzyme-B secreted by CD8+T cells were increased,the cyto-toxicity of CD8+T cells against HeLa cells was enhanced in the CD8+T+Aca-L group,CD8+T+Aca-M group,and CD8+T+Aca-H group(P<0.05),the change trend of corresponding indicators in the CD8+T+H-151 group was opposite to that in the CD8+T+Aca-H group(P<0.05).H-151 reversed the effects of high Aca on the malignant biological behavior of HeLa cells and the immune function of CD8+T cells.Conclusion Aca may inhibit the malignant biological behavior of HeLa cells and enhance the immune function of CD8+T cells by activating the STING/TBK1/IRF3 pathway.

acacetincervical cancerproliferationinvasionimmune

王阳阳、刘耘、程义杰、刘艺文

展开 >

唐山中心医院妇科,河北唐山 067000

唐山中心医院生殖内分泌科,河北唐山 067000

金合欢素 宫颈癌 增殖 侵袭 免疫

2024

中国优生与遗传杂志
中国优生科学协会

中国优生与遗传杂志

CSTPCD
影响因子:0.527
ISSN:1006-9534
年,卷(期):2024.32(11)