Wang Shanshan, Yang Die, Yuan Chengjia, Wu Yang, Wang Qingying, Wu Yongjian, Zhang Xiaochun
Department of Oncology, Yangzhou Hospital of Traditional Chinese Medicine, Yangzhou, Jiangsu, 225002, China.
Clinical Traditional Chinese Medical College, Yangzhou University, Yangzhou, Jiangsu, 225002, China.
Adv Biol (Weinh). 2025 Mar;9(3):e2400306. doi: 10.1002/adbi.202400306. Epub 2025 Feb 6.
Traditional Chinese medicine (TCM) Yi-Fei-Jie-Du-Tang (YFJDT) has shown potential in lung cancer treatment. However, the mechanisms underlying the effects of YFJDT on lung cancer remain unclear. Bioinformatics analysis is conducted to identify potential targets of YFJDT. The impact of YFJDT on hypoxia-inducible factor 1 alpha (HIF1A), ferroptosis, and vasculogenic mimicry (VM) is investigated using xenograft tumor models and A549 cells. Additionally, A549 cells are stimulated with CoCl to mimic the hypoxic microenvironment of the tumor. The role of HIF1A overexpression in modulating ferroptosis is assessed. The effects of HIF1A and ferroptosis on epithelial-mesenchymal transition (EMT) and VM in vitro are evaluated. Results: YFJDT treatment led to a concentration-dependent decrease in HIF1A levels in xenograft tumors and A549 cells. Overexpression of HIF1A counteractes the inhibitory effects of YFJDT on proliferation, EMT, and VM in transplanted tumors. Moreover, HIF1A overexpression attenuates YFJDT-induced lipid peroxidation and iron accumulation, indicating inhibition of ferroptosis in A549 cells. Hypoxia-induced alterations in EMT markers and VM are reversed by YFJDT but exacerbated by HIF1A overexpression. Molecular docking identified salicylic acid and psoralen as potential components of YFJDT targeting HIF1A. YFJDT exerts anti-tumor effects in lung cancer by downregulating HIF1A and promoting ferroptosis.
传统中药益肺解毒汤（YFJDT）在肺癌治疗中已显示出潜力。然而，YFJDT对肺癌作用的潜在机制仍不清楚。进行生物信息学分析以确定YFJDT的潜在靶点。使用异种移植肿瘤模型和A549细胞研究YFJDT对缺氧诱导因子1α（HIF1A）、铁死亡和血管生成拟态（VM）的影响。此外，用CoCl刺激A549细胞以模拟肿瘤的缺氧微环境。评估HIF1A过表达在调节铁死亡中的作用。评估HIF1A和铁死亡对体外上皮-间质转化（EMT）和VM的影响。结果：YFJDT处理导致异种移植肿瘤和A549细胞中HIF1A水平呈浓度依赖性降低。HIF1A的过表达抵消了YFJDT对移植肿瘤增殖、EMT和VM的抑制作用。此外，HIF1A过表达减弱了YFJDT诱导的脂质过氧化和铁积累，表明抑制了A549细胞中的铁死亡。YFJDT可逆转缺氧诱导的EMT标志物和VM的改变，但HIF1A过表达会加剧这种改变。分子对接确定水杨酸和补骨脂素是YFJDT靶向HIF1A的潜在成分。YFJDT通过下调HIF1A和促进铁死亡在肺癌中发挥抗肿瘤作用。
