Lin Xiaoqian, Md Akim Abdah, Jin Zhihai, Abdul Hamid Habibah, Teng Xiaofei, Gu Bo
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia 43400 UPM Serdang, Selangor, Malaysia.
Liupanshui City Women and Child's Health Hospital of Guizhou Province Liupanshui, Guizhou, China.
Am J Cancer Res. 2025 Jul 15;15(7):3003-3016. doi: 10.62347/YMKH5775. eCollection 2025.
TBBPS and TCBPA are increasingly used as alternatives to tetrabromobisphenol A (TBBPA) and have been detected in various environmental samples. Moreover, they have been widely detected in human biological matrices such as blood, milk, . In view of this, it is particularly urgent to comprehensively evaluate the toxicological properties of TBBPS/TCBPA. In this study, in vitro experiments were carried out with cervical cancer cell models and normal cervical cell models. Comprehensive biochemical experiments were conducted to examine the effects of TBBPS and TCBPA on cervical cancer cells. Cell proliferation assays with CCK8 and EdU demonstrated that TBBPS and TCBPA enhance cervical cancer cell proliferation and enhance the expression of proliferation-related molecules. Subsequent research demonstrated that TBBPS/TCBPA enhance the secretion of inflammatory factors in cervical cancer cells, influencing cell proliferation. In the cervical epithelial cell model, our study revealed that TBBPS/TCBPA suppressed the proliferation of normal cervical epithelial cells. Mechanistic studies revealed that TBBPS/TCBPA treatment enhanced ds-DNA release, thereby activating the cGAS-STING signaling pathway and inhibiting cell proliferation. This study concludes that TBBPS/TCBPA exhibit dual effects by promoting cervical cancer cell growth while inhibiting normal cervical cell proliferation, which was mediated through the regulation of the inflammatory response. This study's findings will serve as a foundation for evaluating the potential health risks posed by TCBPA/TBBPS exposure.
双（2,3-二溴丙基）磷酸酯（TBBPS）和三（2,3-二溴丙基）磷酸酯（TCBPA）越来越多地被用作四溴双酚A（TBBPA）的替代品，并且已在各种环境样品中被检测到。此外，它们还在血液、乳汁等多种人体生物基质中被广泛检测到。鉴于此，全面评估TBBPS/TCBPA的毒理学特性尤为迫切。在本研究中，利用宫颈癌细胞模型和正常宫颈细胞模型进行了体外实验。开展了全面的生化实验以检测TBBPS和TCBPA对宫颈癌细胞的影响。采用CCK8和EdU进行的细胞增殖试验表明，TBBPS和TCBPA可促进宫颈癌细胞增殖并增强增殖相关分子的表达。后续研究表明，TBBPS/TCBPA可增强宫颈癌细胞中炎性因子的分泌，从而影响细胞增殖。在宫颈上皮细胞模型中，我们的研究表明TBBPS/TCBPA可抑制正常宫颈上皮细胞的增殖。机制研究表明，TBBPS/TCBPA处理可增强双链DNA释放，从而激活cGAS-STING信号通路并抑制细胞增殖。本研究得出结论，TBBPS/TCBPA通过促进宫颈癌细胞生长同时抑制正常宫颈细胞增殖而表现出双重作用，这是通过炎症反应的调节介导的。本研究结果将为评估TCBPA/TBBPS暴露所带来的潜在健康风险奠定基础。
