Open Access

ARTICLE

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

Ashuai Du^1,#, Dianbin Guo^2,#, Dongbo Yuan^3,#, Kai Li⁴, Yuanyuan Luo⁴, Songsong Tan³, Xuchao Dai⁴, Bo Yu⁵, Wanxiang You⁶, Junjie Zhao⁷, Bo Yan³, Kehua Jiang^3,*, Xiaofei Fan^2,*, Jianguo Zhu^3,*,*

1 Department of Infection, Guizhou Provincial People’s Hospital, Guiyang, China
2 Shandong Medical College, No. 5460, Second Ring South Road, Jinan, China
3 Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, China
4 Department of Urology, GuiZhou University Medical College, Guiyang, China
5 Graduate School, Zunyi Medical University, Zunyi, China
6 Department of Urology, Dejiang County People’s Hospital of Guizhou Province, Dejiang, China
7 Yantai Yuhuangding Hospital, Yantai, China

* Corresponding Authors: Kehua Jiang. Email: " />; Xiaofei Fan. Email: ; Jianguo Zhu. Email: " />,
# These authors contributed equally to this work

Oncology Research 2026, 34(5), 35 https://doi.org/10.32604/or.2026.076716

Received 25 November 2025; Accepted 14 February 2026; Issue published 22 April 2026

Abstract

Background: 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. Methods: 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 in vivo mouse model was used to assess the impact of BPA exposure and PI3K inhibition on tumor progression. Results: 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 in vitro and reduced tumor progression in vivo. Conclusions: 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.

---

Keywords

---