Regulation of Th1/Th2 immune balance by shikonin via STING in Lewis lung carcinoma mice

Objective To investigate the effects of shikonin (SK) on Th1/Th2 immune balance in Lewis lung cancer-bearing mice via STING.Methods A lung cancer tumor-bearing mouse model was established. Mice were randomly divided into six groups: normal control (NC), model (PBS), low-dose SK (SK-L), medium-dose SK (SK-M), high-dose SK (SK-H), medium-dose SK plus STING inhibitor (SK-M+C176), and control (PTX), with six mice per group. Administration began on day 7 post-tumor implantation, with alternate-day dosing. Mice were sacrificed on day 28 post-implantation to record survival and tumor progression, plotting tumor volume growth curves and tumor-bearing mouse survival curves. Calculate spleen and thymus indices. Flow cytometry detects STING expression in splenic dendritic cells (DCs), surface molecules MHCII, CD80, CD86, chemokine receptors CXCR4, CCR5, CCR7, and T cell subset expression levels (CD3+T, CD4+T, CD8+T, Th1, Th2). Detect concentrations of IFN-β, IL-12, IFN-γ, TNF-α, IL-4, VEGF, Gzms-B and PF in mouse ocular blood serum via ELISA.Results Compared with the model group, the SK medium and high dose group delayed tumor growth and prolonged survival in mice (P<0.01); increased spleen and thymus indices (P<0.01); upregulated STING, surface molecules MHCII, CD80, CD86, and chemokines CXCR4 and CCR7 expression in splenic dendritic cells (DCs), while downregulating CCR5 expression (P<0.01); increased the proportion of CD4+T cells and the CD4+T/CD8+T ratio in the spleen; upregulated Th1 expression while downregulating Th2 expression in splenic CD4+T lymphocytes, promoting Th1/Th2 balance (P<0.01); Increased serum concentrations of IFN-β, IL-12, IFN-γ, TNF-α, Gzms-B, and PF in mice while decreasing IL-4 and VEGF levels (P<0.05); Compared with the SK-M group, the SK-M+C176 group reversed the suppression of tumor progression in Lewis tumor-bearing mice by SK and its promotion of STING, DC, and Th1 cell activation (P<0.05).Conclusion SK delays tumor growth and prolongs survival in tumor-bearing mice by enhancing immune cell functions to exert antitumor immune effects. This mechanism may involve upregulating STING expression in DCs, promoting DC maturation and migration, enhancing antigen presentation capacity, and thereby shifting the Th1/Th2 balance toward Th1 dominance.