Bedolla Nuran, Liu Linyu, Liu Xueting, Xie Qiuxian, Ren Yanli
College of Biological Sciences and Technology, YiLi Normal University, China.
College of Biological Sciences and Technology, YiLi Normal University, China.
Toxicon. 2025 Feb;255:108233. doi: 10.1016/j.toxicon.2025.108233. Epub 2025 Jan 7.
Radiotherapy is essential for the management of esophageal squamous cell carcinoma (ESCC). However, ESCC cells are highly susceptible to developing resistance to radiotherapy, leading to poor prognosis. Ursolic acid (UA) is a herbal monomer, has multiple medicinal benefits like anti-tumor. The impact of UA on the sensitivity of ESCC cells to radiotherapy is currently unclear.
The impact of UA and ionizing radiation (IR) on the viability of TE-1 and KYSE30 cells was assessed by the MTT assay. EdU staining, flow cytometry, clone formation, Wound healing and Transwell assay detected the biological properties of ESCC cells. FerroOrange, DCFH-DA, and kits to detect the influences of UA and/or IR treatment on cellular ferroptosis. The levels of p53/solute carrier family 7a member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway proteins were detected by Western blot. Additionally, a subcutaneous graft tumor model was constructed in nude mice.
10 μM UA reduced the viability and induced death of ESCC cells. UA enhanced the impacts of IR by suppressing cell proliferation, migration and invasion, inducing cell death, and causing cell cycle arrest. Ferroptosis inhibitor impaired the inhibitory impacts of UA and IR on the biological properties of ESCC cells. The combination of UA and IR led to ferroptosis through the modulation of the p53/SLC7A11/GPX4 pathway, and UA enhanced the responsiveness of ESCC cells to IR both in vitro and in vivo.
UA inhibits the malignant biological behavior of ESCC by modulating ferroptosis through the p53/SLC7A11/GPX4 pathway, and enhances the sensitivity of ESCC cells to IR.
放射治疗是食管鳞状细胞癌（ESCC）治疗的重要组成部分。然而，ESCC细胞对放射治疗极易产生耐药性，导致预后不良。熊果酸（UA）是一种草药单体，具有多种药用功效，如抗肿瘤。目前尚不清楚UA对ESCC细胞放射敏感性的影响。
采用MTT法评估UA和电离辐射（IR）对TE-1和KYSE30细胞活力的影响。EdU染色、流式细胞术、克隆形成、伤口愈合和Transwell实验检测ESCC细胞的生物学特性。使用FerroOrange、DCFH-DA和试剂盒检测UA和/或IR处理对细胞铁死亡的影响。通过蛋白质免疫印迹法检测p53/溶质载体家族7a成员11（SLC7A11）/谷胱甘肽过氧化物酶4（GPX4）通路蛋白的水平。此外，在裸鼠中构建皮下移植瘤模型。
10 μM UA可降低ESCC细胞的活力并诱导其死亡。UA通过抑制细胞增殖、迁移和侵袭、诱导细胞死亡以及导致细胞周期停滞来增强IR的作用。铁死亡抑制剂削弱了UA和IR对ESCC细胞生物学特性的抑制作用。UA和IR的联合作用通过调节p53/SLC7A11/GPX4通路导致铁死亡，并且UA在体外和体内均增强了ESCC细胞对IR的反应性。
UA通过p53/SLC7A11/GPX4通路调节铁死亡来抑制ESCC的恶性生物学行为，并增强ESCC细胞对IR的敏感性。
