Silica nanoparticle-delivered astragaloside IV promotes oxidative stress and apoptosis in prostate cancer cells via the miR-125-5p/STIR4 axis

Abstract: Background: Prostate cancer (PCa) treatment is limited by drug resistance and toxicity. Astragaloside IV (AIV) has anti-tumor activity but poor bioavailability. Objectives: To prepare silica nanoparticle-loaded astragaloside IV (SN-AIV) and to investigate whether it induces oxidative stress and apoptosis in PC-3 cells via the miR-125-5p/STIR4 axis. Methods: SN-AIV was prepared and characterized. PC-3 cells were treated with SN-AIV, free AIV, or controls. Cell viability, apoptosis, mitochondrial function and oxidative stress markers were assessed. qRT-PCR and Western blot detected miR-125-5p and STIR4 expression. A dual-luciferase reporter assay confirmed target binding. Functional rescue experiments were performed. Results: SN-AIV exhibited uniform size (98.4 ± 6.2 nm) and sustained release. Compared with controls, SN-AIV significantly reduced cell viability, induced apoptosis, decreased mitochondrial membrane potential, increased MDA and decreased SOD and GSH levels. SN-AIV up-regulated miR-125-5p and down-regulated STIR4. STIR4 was confirmed as a direct target of miR-125-5p. miR-125-5p overexpression or STIR4 knockdown mimicked SN-AIV effects, while miR-125-5p inhibition reversed them. Conclusion: SN-AIV induces oxidative stress and apoptosis in PC-3 cells by up-regulating miR-125-5p and down-regulating STIR4, providing an experimental basis for nanoparticle-delivered AIV in PCa treatment.