Mechanism of Shenbai Fuzheng granule in regulating tumor immune response via cGAS-STING pathway
Objective It is to explore the mechanism of Shenbai Fuzheng granule in regulating tumor immune response via cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)pathway.Methods Sixty KM mice were taken to establish human gastric cancer MGC803 cell transplantation tumor models,and the 42 successfully modeled mice were divided into 10 mice in the model group,10 mice in the Shenbai Fuzheng low-dose group,11 mice in the Shenbai Fuzheng middle-dose group,and 11 mice in the Shenbai Fuzheng high-dose group according to randomized numerical table,and were respectively given physiological saline,and 5 mg/g,10 mg/g,and 20 mg/g of Shenbai Fuzheng granules by gavage,twice daily,continuously treated for 15 days.At the end of the final gavage,the tumor tissues were peeled off,weighed and the tumor inhibition rate was calculated,the pathological morphology of the tumor tissues was observed by HE staining,and the levels of immune activation indexes[CD4+,CD8+,γ-interferon(IFN-γ),tumor necrosis factor-α(TNF-α),CD45+CD11c+MHC-Ⅱ+,CD40+,CD70+,CD4+ Foxp3+ Treg]were detected by flow cytometry,the levels of cGAS-STING pathway-related cytokines[β-interferon(IFN-β),C-C chemokine 22(CCL22),C-C chemokine 17(CCL17),and interleukin-10(IL-10)]in tumor tissues were detected by ELISA,and the expressions of cGAS-STING pathway-relat-ed proteins[STING,TANK-binding kinase 1(TBK1),interferon regulatory factor 3(IRF3)]in tumor tissues were detec-ted by Western blot.Results The tumor weight of each Shenbai Fuzheng group was significantly lower than that of the model group(all P＜0.05),and the tumor weight decreased while the tumor inhibition rate increased with the increase of the dose of Shenbai Fuzheng granules,and the differences were all statistically significant(all P＜0.05).The inflammatory infiltration of the gastric mucosa and congestion and edema of the intercellular stroma of the mice in each Shenbai Fuzheng group were improved to different degrees with no obvious anisotropy compared with that of the model group.The levels of CD4+,CD8+,IFN-γ,CD45+CD11c+MHC-II+,CD40+,CD70+,and the relative expressions of cGAS,STING,TBK1 and IRF3 proteins in the tumor tissues of mice in each Shenbai Fuzheng group were significantly higher than those in the model group(all P＜0.05),and the above indexes increased with the increase of dosage of Shenbai Fuzheng granules(all P＜0.05).The levels of TNF-α,CD4+Foxp3+Treg,IFN-β,CCL22,CCL17,IL-10 in the tumor tissues of mice in each Shenbai Fuzheng group were significantly lower than those in the model group(all P＜0.05),and the levels of the above indexes decreased with the increase of the dosage of Shenbai Fuzheng granules(all P＜0.05).Conclusion Shenbai Fuzheng granules can inhibit tumor growth in mice with transplanted tumors of gastric cancer,can enhance the immune function and attenuate the inflammatory response of mice by regulating the tumor immune response,the mechanism of which may be related to the regulation of the cGAS-STING pathway.
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