TY  - EJOU
AU  - Du, Ashuai 
AU  - Guo, Dianbin 
AU  - Yuan, Dongbo 
AU  - Li, Kai 
AU  - Luo, Yuanyuan 
AU  - Tan, Songsong 
AU  - Dai, Xuchao 
AU  - Yu, Bo 
AU  - You, Wanxiang 
AU  - Zhao, Junjie 
AU  - Yan, Bo 
AU  - Jiang, Kehua 
AU  - Fan, Xiaofei 
AU  - Zhu, Jianguo 

TI  - Elucidating the Potential Targets and Mechanisms of Bisphenol A-Induced Prostate Cancer Based on Network Toxicology and Molecular Docking Analyses
T2  - Oncology Research

PY  - 2026
VL  - 34
IS  - 5
SN  - 1555-3906

AB  -  <b>Background:</b> Bisphenol A (BPA) is a widely used industrial chemical and endocrine-disrupting compound, and accumulating evidence suggests that it may contribute to prostate cancer progression; however, the underlying molecular mechanisms remain incompletely elucidated. This study aimed to elucidate the molecular targets and signaling pathways underlying BPA-induced prostate cancer progression. <b>Methods:</b> In this study, an integrated strategy combining network toxicology, molecular docking, and molecular dynamics simulations was employed to identify potential BPA-related targets and signaling pathways involved in prostate cancer. Candidate targets were retrieved from public databases, followed by protein-protein interaction network analysis to screen key hub genes. Functional assays were performed to evaluate the effects of BPA on prostate cancer cell migration, invasion, epithelial-mesenchymal transition (EMT), and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling, and an <i>in vivo</i> mouse model was used to assess the impact of BPA exposure and PI3K inhibition on tumor progression. <b>Results:</b> Eighteen BPA-related core targets were identified, among which androgen receptor (AR), matrix metalloproteinase 9 (MMP9), matrix metalloproteinase 2 (MMP2), kallikrein-related peptidase 3 (KLK3), and hypoxia-inducible factor 1 alpha (HIF1A) emerged as key hub genes. Computational analyses indicated stable predicted interactions between BPA and these proteins. Functionally, BPA exposure promoted prostate cancer cell invasion and EMT, which were associated with activation of the PI3K/AKT and MMP signaling pathways, whereas the PI3K inhibitor LY294002 effectively attenuated BPA-induced invasive phenotypes <i>in vitro</i> and reduced tumor progression <i>in vivo</i>. <b>Conclusions:</b> Collectively, these findings provide mechanistic insights into BPA-driven prostate cancer progression and highlight the value of network toxicology-based approaches in environmental toxicology research.
KW  - Bisphenol A; prostate cancer; network toxicology; phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling; LY294002

DO  - 10.32604/or.2026.076716