Astragaloside IV inhibits nasopharyngeal carcinoma progression by inhibiting SATB2/Wnt/PD-L1 pathway and enhancing the killing activity of T cells.

Astragaloside IV (AS IV) inhibits the malignant phenotype of nasopharyngeal carcinoma (NPC), but whether its mechanism involves the regulation of immune checkpoint programmed cell death-ligand 1 (PD-L1) is not clear. Human NPC cells were treated with AS IV. The effects of AS IV on PD-L1 expression were assessed using RT-qPCR and Western blot. SATB2/Wnt/β-catenin signaling axis regulation was analyzed by siRNA interference, plasmid overexpression and Wnt pathway inhibitor DKK-1. T cell killing activity and tumor malignant phenotype were evaluated by LDH release, ELISA, flow cytometry and Transwell experiments. huHSC-NCG tumor-bearing mice were established to detect tumor growth, immune cell infiltration and related protein expression. AS IV dose-dependently inhibited PD-L1 expressions within NPC cells, and enhanced the activation and killing function of CD8+ T cells. Mechanism studies have shown that AS IV significantly lowered the expression of SATB2, thereby inhibiting Wnt/β-catenin axis and c-MYC and Axin2 expressions, and ultimately reducing PD-L1 levels. Overexpression of SATB2 reversed AS IV's suppression of this signaling and PD-L1. Animal experiments confirmed that AS IV effectively inhibited tumor growth, enhanced CD8+ T cell infiltration and activity within tumor tissues, and down-regulated the SATB2/β-catenin/PD-L1 signal axis. AS IV inhibited PD-L1 expression in NPC via targeting the SATB2/Wnt/β-catenin axis, thereby activating CD8+ T cells, amplifying immunological responses, and ultimately inhibiting NPC growth. Graphical Abstract.