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