Shenling Qige Granules inhibit esophageal squamous cell carcinoma progression in TE-1 xenograft and cell-based models by modulating the DCN-TGF-β/Smad signaling axis.

Shenling Qige Granules (SLQG), derived from the Qing Dynasty formula Qige San recorded in Yi Xue Xin Wu, has been used in clinical practice in China as an adjuvant traditional Chinese medicine preparation for esophageal squamous cell carcinoma (ESCC), but its molecular basis remains unclear. This study investigated the antitumor effects and mechanisms of SLQG using TE-1 xenograft mice and SLQG-containing serum-treated TE-1 cells. Transcriptome sequencing, network pharmacology, molecular docking, molecular dynamics simulation, and public-database analysis were integrated to prioritize candidate mechanisms. Histological, molecular, cellular, and siRNA-mediated decorin (DCN) knockdown assays were performed for validation. SLQG, especially at the medium dose, inhibited xenograft tumor growth and increased DCN expression. Transcriptomic analysis highlighted the transforming growth factor-β (TGF-β)/Smad pathway. In silico analyses suggested that several SLQG-derived compounds, particularly ursolic acid, may be associated with DCN-related regulation. Public-database analysis indicated lower DCN expression in esophageal carcinoma tumor samples than in normal samples and an association with pathological stage. In vivo and in vitro, SLQG increased DCN expression, reduced Smad2/3 phosphorylation, promoted pro-apoptotic signaling, and induced G0/G1 arrest; these effects were attenuated by DCN knockdown. These findings suggest that SLQG inhibited ESCC progression in TE-1 xenograft and cell-based models, potentially through modulation of the DCN-associated TGF-β/Smad signaling axis.