Qianlie Xiaozheng Formula Inhibits Prostate Cancer via the STING/TBK1/IRF3 Pathway by Suppressing CHK1.

Abstract

Qianlie Xiaozheng formula (QLXZF), a multi-herbal TCM prescription, has demonstrated clinical efficacy against prostate cancer (PCa), but its immunomodulatory mechanisms remain elusive. This study aims to explore the molecular mechanisms of QLXZF's inhibitory effects on PCa. Tumor-bearing mouse model and an RM-1 tumor cell model co-cultured with CD8T cells are treated with QLXZF. Mechanistic studies integrated in vivo imaging, IHC, WB, and genetic interventions (CHK1 overexpression). In the mouse model, QLXZF dose-dependently suppressed tumor growth (p<.01) without visceral toxicity. Immunofluorescence experiments showed QLXZF treatment has decreased the expression of CHK1, increased γH2AX foci formation. Western blot experiments confirmed an increase in pSTING/STING, pTBK1/TBK1, and pIRF3/IRF3 ratio. Additionally, the use of QLXZF increased the levels of CCL5 and CXCL10. In vitro cell experiments showed results consistent with those in the in vivo model. Further studies indicated that overexpression of CHK1 abolished the suppressive effects of QLXZF on prostate cancer cells. The study suggests that QLXZF may inhibit CHK1 expression, induce DNA image accumulation, and activate the STING/TBK1/IRF3 pathway to promote CD8⁺T cell recruitment. These findings provide a new mechanistic basis for the application of QLXZF in the treatment of PCa.