Chen Xiang, Lu Jun-Lin, Li Hong, Liu Guang-Yao, Li Ting-Ting, Xiao Kang-Hua, Ye Hai-Shan, Li Sheng, Chen Xu, Liu Jia
School of Medicine, South China University of Technology, Guangzhou 510006, China.
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China.
J Cancer. 2025 Jun 9;16(8):2613-2625. doi: 10.7150/jca.109350. eCollection 2025.
Resveratrol (RES) exhibits promising anti-bladder cancer (BC) effects. It causes cell death of BC cell lines and xenografts, but comprehensive analyses are required concerning oxidative status in RES-treated BC cells and its relevance with cell death patterns, and especially the efficacy of BC individuals. Two human BC cell lines (T24 and UM-UC-3) were cultured under 2D and 3D conditions to determine RES IC values and 100 μM RES was thus used as a working concentration to treat 18 cases of BC-derived organoids (BCDOs). To observe the experimental results, this study will assess the oxidative stress status of bladder cancer cells, the corresponding potential cell death patterns, and the extent of inhibition by death inhibitors. It revealed growth suppression of 10 RES-treated BCDOs (55.56%), accompanied by reduced mitochondrial potential and increased Reactive Oxygen Species (ROS) levels. Lipid peroxidation and downregulation of GPX4 and xCT, key antioxidant molecules of ferroptosis, were also found in RES-sensitive BC cells, and the inhibition rate of ferroptosis inhibitors increased to 22.57% of BCDOs. In addition, the supplementary experiment also indicated that it may be related to apoptosis and autophagy pathways. The above cellular and molecular alterations were not distinct in RES-insensitive BCDOs. RES possesses promising inhibitory effects on either BC cell lines or a large part (10/18) of BCDOs via enhancing oxidative stress and triggering the ferroptosis pathway or more. These findings underscore anti-BC properties of RES and its role as a potential personalized treatment option.
白藜芦醇（RES）展现出有前景的抗膀胱癌（BC）作用。它能导致膀胱癌细胞系和异种移植瘤的细胞死亡，但需要对RES处理的膀胱癌细胞中的氧化状态及其与细胞死亡模式的相关性，尤其是对膀胱癌个体的疗效进行全面分析。将两个人膀胱癌细胞系（T24和UM-UC-3）在二维和三维条件下培养以确定RES的半数抑制浓度（IC值），因此使用100μM RES作为工作浓度来处理18例膀胱癌来源的类器官（BCDOs）。为观察实验结果，本研究将评估膀胱癌细胞的氧化应激状态、相应的潜在细胞死亡模式以及死亡抑制剂的抑制程度。结果显示，10个经RES处理的BCDOs生长受到抑制（55.56%），同时线粒体电位降低，活性氧（ROS）水平升高。在对RES敏感的膀胱癌细胞中还发现了脂质过氧化以及铁死亡关键抗氧化分子谷胱甘肽过氧化物酶4（GPX4）和胱氨酸/谷氨酸逆向转运体（xCT）的下调，铁死亡抑制剂对BCDOs的抑制率增至22.57%。此外，补充实验还表明其可能与凋亡和自噬途径有关。上述细胞和分子改变在对RES不敏感的BCDOs中并不明显。RES通过增强氧化应激并触发铁死亡途径等，对膀胱癌细胞系或大部分（10/18）的BCDOs具有有前景的抑制作用。这些发现强调了RES的抗膀胱癌特性及其作为潜在个性化治疗选择的作用。
