Se@SiO 2 @mSiO 2 nanoparticle inhibits cellular oxidative stress and Wnt/β-catenin pathway by inhibiting AGGF1 expression in the treatment of prosta
Jingcheng Lyu, Mingyu Chang, Lianhui Sun, Ruiyu Yue, Xijian Liu, Guangjian Fan, Aihong Chen, Wei Huang, Ye Tian, Boyu YangAbstract
Background and Objective
Advances in nanomedicine have introduced promising strategies for enhancing drug bioavailability, tumor targeting, and controlled release. This study aimed to investigate the regulatory role of angiogenic factor with G patch and FHA domains 1 (AGGF1) in prostate cancer progression and to evaluate the therapeutic potential of a double-layered silica-shelled selenium nanoparticle (Se@SiO 2 @mSiO 2 ) targeting the AGGF1-associated signaling network.
Methods
We performed bioinformatics analyses based on the TCGA-PRAD dataset, including differential expression analysis, WGCNA, and functional enrichment, to identify AGGF1-related pathways. Clinical specimens from 54 prostate cancer patients were collected for validation through Western Blot and immunohistochemistry. We synthesized Se@ SiO 2 @mSiO 2 via a double-layer coating technique and characterized its physicochemical properties by TEM, XRD, XPS, and selenium release assays. To assess the anti-tumor effects of Se@SiO 2 @mSiO 2 , we employed CCK-8, colony formation assays, oxidative stress detection, and established both subcutaneous and orthotopic tumor models in BALB/c nude mice. We further conducted ChIP-qPCR and gene overexpression/silencing experiments to delineate the upstream-downstream relationship between AGGF1 and the Wnt/β-catenin pathway.
Results
AGGF1 was significantly overexpressed in prostate cancer tissues compared with adjacent normal tissues, and high AGGF1 expression was associated with advanced tumor stage, higher Gleason score, and poorer disease-free and overall survival. Se@SiO 2 @mSiO 2 exhibited a sustained selenium release profile and demonstrated effective intracellular uptake. Treatment with Se@SiO 2 @mSiO 2 inhibited prostate cancer cell proliferation in a concentration-and time-dependent manner, reduced AGGF1 expression, suppressed oxidative damage, and downregulated β-catenin expression. Overexpression of AGGF1 partially reversed the anti-proliferative effects and Wnt/β-catenin pathway inhibition induced by Se@SiO 2 @mSiO 2 , whereas silencing β-catenin did not significantly alter AGGF1 expression, supporting the upstream regulatory position of AGGF1. In vivo experiments confirmed that Se@SiO 2 @mSiO 2 significantly reduced tumor burden without detectable organ toxicity.
Conclusion
AGGF1 functions as an upstream regulator connecting oxidative stress and Wnt/β-catenin signaling in prostate cancer. Se@SiO 2 @mSiO 2 exerts anti-tumor effects by downregulating AGGF1 and subsequently suppressing both pathways. These findings position AGGF1 as a pivotal therapeutic target and validate Se@SiO 2 @mSiO 2 as a candidate nanomedicine for precision treatment of prostate cancer.