Astragaloside IV inhibits nasopharyngeal carcinoma progression by suppressing the SATB2/Wnt signaling axis.

Abstract

Astragaloside IV (AS-IV), a major bioactive component of Astragalus membranaceus, exhibits anti-cancer and anti-inflammatory properties. However, its precise role in nasopharyngeal carcinoma (NPC) remains unclear. This study investigated the effects of AS-IV on NPC progression and its relationship with Special AT-rich binding protein-2 (SATB2), a diagnostic marker for NPC. AS-IV treatment reduced NPC cell viability in a dose-dependent manner, as assessed by CCK-8 assays. Functional experiments, including transwell, immunofluorescence, and flow cytometry assays, demonstrated that AS-IV inhibited cell migration, invasion, and autophagy while promoting apoptosis. Western blot analysis showed that SATB2 expression was significantly elevated in NPC cells, particularly in C666-1 and HK-1 cells. Overexpression of SATB2 partially reversed AS-IV's inhibitory effects on NPC progression. Further analysis revealed that AS-IV suppressed the Wnt signaling pathway by downregulating SATB2 expression, while SATB2 overexpression restored Wnt pathway activation. This effect was reversed upon treatment with the Wnt pathway inhibitor DKK-1. In vivo, AS-IV administration inhibited tumor growth in a nude mouse subcutaneous xenograft model, reduced Ki-67 positivity, and lowered LC3B expression, indicating decreased proliferation and autophagy. However, these effects were diminished upon SATB2 overexpression. These findings suggest that AS-IV exerts anti-tumor effects in NPC by downregulating SATB2 and suppressing Wnt pathway activation, highlighting its potential as a therapeutic agent for NPC.

Highlights: Astragaloside IV (AS-IV) reduces nasopharyngeal carcinoma (NPC) cell vitality, suppresses cell migration, invasion and autophagy, and fosters apoptosis.SATB2 exhibits notably high levels in NPC cells.Overexpression of SATB2 counteracts the inhibition of NPC malignant progression by AS-IV.AS-IV impedes NPC progression by decreasing SATB2 and thereby hindering the Wnt pathway.AS-IV deters NPC tumor growth in nude mice.