[Effect and mechanism of Guiqi Yiyuan Ointment combined with cisplatin against lung cancer by regulating Th1/Th2 immune imbalance via cGAS-STING pathway].

This paper aims to investigate the tumor-inhibitory effect and underlying mechanism of Guiqi Yiyuan Ointment combined with cisplatin on Lewis lung cancer tumor-bearing mice based on the cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING) signaling pathway. A Lewis lung cancer tumor-bearing mouse model was established, and the successfully modeled mice were randomly divided into a model group, a cisplatin group, a cisplatin + TCM group, an inhibitor group, an inhibitor + TCM group, and a blank group, with 10 mice in each group. Corresponding interventions were administered to mice in each group for two weeks. Routine blood tests were performed to detect the levels of white blood cells(WBC), red blood cells(RBC), and platelets(PLT) in the peripheral blood of mice; the tumor inhibition rate and the organ indices were calculated; hematoxylin-eosin(HE) staining was used to observe the pathological morphology of tumor tissue; flow cytometry was adopted to detect the proportions of CD4~+ and CD8~+ T lymphocytes in the spleen; enzyme-linked immunosorbent assay was employed to measure the contents of interleukin-4(IL-4) and interferon-γ(IFN-γ) in serum; immunohistochemistry was used to detect the expressions of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in tumor tissue; immunofluorescence was applied to detect the expression of interferon-β(IFN-β) in tumor tissue; quantitative polymerase chain reaction(Q-PCR) was used to determine the mRNA expressions of cGAS, STING, and TANK-binding kinase 1(TBK1) in tumor tissue; Western blot(WB) was performed to detect the protein expressions of cGAS, STING, TBK1, interferon regulatory factor 3(IRF3), and phosphorylated-interferon regulatory factor 3(p-IRF3) in tumor tissue. The results show that compared with those in the cisplatin group, the levels of the peripheral blood, the tumor inhibition rate, and the organ indices of mice in the cisplatin + TCM group are significantly increased; pathological damages such as a large number of apoptosis and nuclear fragmentation are observed in tumor tissue; the proportions of T lymphocytes are significantly increased; the content of IFN-γ is significantly increased while the content of IL-4 is decreased; the expression of IL-6 is attenuated; the expression of TNF-α and the fluorescent expression of IFN-β are significantly increased; the mRNA expression levels of cGAS, STING, and TBK1 as well as the protein expression levels of cGAS, STING, TBK1, IRF3, and p-IRF3 are significantly up-regulated. In conclusion, Guiqi Yiyuan Ointment may inhibit tumor growth by regulating the expressions of key molecules in the cGAS-STING signaling pathway and promoting the secretion of downstream IFN-β, thereby reversing Th1/Th2 immune imbalance and restoring the anti-tumor immune response.