Li Jing, Zhu Ziyi, Ni Jing, Ye Lizi, Huang Xiaoyan, Jing Dong, Lu Yanhong, Yue Ling
Department of Endocrinology, The General Hospital of Central Theater Command, Wuhan, 430070, China; The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510180, China.
Suzhou Xiangcheng District Integrated Chinese and Western Medicine Hospital, Suzhou 215137, Jiangsu, China.
Arch Biochem Biophys. 2025 Sep;771:110481. doi: 10.1016/j.abb.2025.110481. Epub 2025 May 26.
Nrf2 is highly expressed in papillary thyroid cancer (PTC) and is associated with negative outcomes. Research has indicated that Berberine (BBR) can lower Nrf2 levels and trigger apoptosis in cancer cells. However, the exact molecular mechanisms behind its anticancer effects in PTC are not fully understood.
The effects of BBR on cell apoptosis were assessed using the MTT assay and flow cytometry. To evaluate BBR's in vivo antitumor efficacy, a xenograft model was used. Molecular and biochemical methods were applied to clarify the mechanisms through which BBR exerts its anticancer effects in PTC.
BBR has been shown to effectively inhibit the growth of PTC cells and promote programmed cell death. A higher dose of BBR administered via gavage significantly reduced the development of xenograft tumors. Mechanistically, BBR inhibits the Nrf2-dependent pathway of PI3K/Akt signaling pathway, resulting in the production of reactive oxygen species (ROS).
Our results suggest indicate that BBR can target PTC by inhibiting the Nrf2 and PI3K/Akt pathways through ROS generation. This indicats that BBR may serve as a potential therapeutic agent for PTC treatment.
Nrf2在甲状腺乳头状癌（PTC）中高表达，并与不良预后相关。研究表明，黄连素（BBR）可降低Nrf2水平并触发癌细胞凋亡。然而，其在PTC中抗癌作用的确切分子机制尚未完全明确。
采用MTT法和流式细胞术评估BBR对细胞凋亡的影响。为评估BBR的体内抗肿瘤疗效，使用了异种移植模型。应用分子和生化方法阐明BBR在PTC中发挥抗癌作用的机制。
已证明BBR可有效抑制PTC细胞生长并促进程序性细胞死亡。通过灌胃给予较高剂量的BBR可显著减少异种移植肿瘤的生长。机制上，BBR抑制PI3K/Akt信号通路的Nrf2依赖性途径，导致活性氧（ROS）的产生。
我们的结果表明，BBR可通过ROS生成抑制Nrf2和PI3K/Akt途径来靶向PTC。这表明BBR可能作为PTC治疗的潜在治疗药物。
