Assessing the role of bisphenol A in female reproductive cancers using network toxicology, molecular dynamics, and preliminary experimental validation.
Bisphenol A (BPA)-a prevalent environmental contaminant commonly found in plastics-has potential adverse effects on human health. Despite its widespread use, the toxicological mechanisms of BPA in gynecological cancers remain unclear. This study aimed to investigate the potential role of BPA in cervical, endometrial, and ovarian cancers using network toxicology, molecular docking, and molecular dynamics simulations. We identified 683 potential targets of BPA, as well as 496, 207, and 344 overlapping genes associated with cervical, endometrial, and ovarian cancers, respectively. The key genes CXCL8 and MMP9 were consistently upregulated in all three cancers. Molecular docking analysis revealed significant binding affinities of BPA to CXCL8 (-6.5 kcal/mol) and MMP9 (-8.5 kcal/mol). Molecular dynamics simulations further confirmed the stability of these interactions, indicating that BPA may promote the development and progression of gynecological tumors through these targets. The regulation of MMP9, CXCL8, TNF, ESR1, UBA52, and PTGS2 expression by BPA was also demonstrated by RT-PCR and Western blot assays. In addition, the effects of MMP9 and CXCL8 on the migration of female reproductive cancer cells were successfully validated by Transwell. This study highlights the utility of network toxicology in understanding the mechanisms of environmental pollutants and emphasizes the need for further investigations into the effects of BPA exposure.