Abstract

Feiwei Mixture (FWHJ), a hospital preparation for lung cancer, lacks a defined mechanism of action. Using Lewis lung carcinoma (LLC) tumor-bearing mice and an LLC-CD8 + T cell co-culture model, we evaluated the effects of FWHJ on tumor growth, T cell infiltration, and apoptosis. Key signaling molecules (NR1D1, cGAS-STING, SOCS3-JAK-STAT3) and chemokines were analyzed using Western blot, flow cytometry, and immunoassays. Further knockout of NR1D1 confirmed its critical role in mediating the anti-tumor effects of FWHJ. FWHJ dose-dependently inhibited tumor growth in mice and enhanced CD4 + /CD8 + T cell infiltration. It upregulated NR1D1, SOCS3, and the cGAS-STING pathway, while suppressing JAK-STAT3 signaling, leading to increased CCL5, CXCL10, and IFN-α. In co-culture model, FWHJ-containing serum promoted LLC cell apoptosis and suppressed malignant progression, recapitulating the signaling alterations observed in vivo. Crucially, NR1D1 knockout abolished the therapeutic effects of FWHJ. FWHJ inhibits non-small cell lung cancer (NSCLC) by activating NR1D1 to stimulate the cGAS-STING pathway and suppress the JAK-STAT3 signaling axis, thereby enhancing anti-tumor immunity. This study provides a foundation for further investigation into the anti-tumor mechanisms of FWHJ and establishes a scientific basis for its potential application in lung cancer therapy.