Department of General Surgery, Wuhan Third Hospital, Wuhan, Hubei, China.
Department of Neurosurgery, Wuhan Third Hospital, Wuhan, Hubei, China.
Turk J Gastroenterol. 2024 Jul 3;35(8):625-33. doi: 10.5152/tjg.2024.23526.
As a very common malignancy of the digestive system, the incidence and mortality rates of gastric cancer (GC) are increasing year by year. The critical role of ferroptosis in cancer development has been well-documented. The polyphenol compound curcumin shows prominent anti-tumor effects in multiple cancer types, including GC. However, whether curcumin participates in GC tumorigenesis by regulating ferroptosis remains unknown. Gastric cancer cells AGS and HGC-27 were treated with curcumin (0, 10, and 20 μM). Cell viability and death were evaluated through CCK-8 and LDH release assays. LC3B expression in cells was estimated through immunofluorescence staining. Intracellular ferrous iron (Fe2+), GSH, MDA, and lipid ROS levels were assessed by corresponding assay kits. The cellular levels of autophagy markers (ATG5, ATG7, Beclin 1, and LC3B), ferroptosis markers (ACSL4, SLC7A11, and GPX4), and phosphorylated (p)-PI3K, p-AKT, and p-mTOR were determined through western blotting. Curcumin attenuated cell viability but stimulated cell death in GC cells. Curcumin enhanced autophagy in GC cells, as demonstrated by the increased levels of ATG5, ATG7, Beclin 1, and LC3B. Besides, curcumin upregulated iron, MDA, GSH, and ACSL4 levels while downregulated lipid ROS, SLC7A11, and GPX4 levels, suggesting its stimulation on ferroptosis in GC cells. Curcumin decreased p-PI3K, p-AKT, and p-mTOR levels in cells. Importantly, the ferroptosis inhibitor ferrostatin-1 overturned the impacts of curcumin on GC cell viability, death, and ferroptosis. Curcumin suppresses GC development by inducing autophagy-mediated ferroptosis by inactivating the PI3K/AKT/mTOR signaling.
作为一种非常常见的消化系统恶性肿瘤，胃癌（GC）的发病率和死亡率逐年上升。铁死亡在癌症发展中的关键作用已得到充分证实。多酚化合物姜黄素在多种癌症类型中表现出显著的抗肿瘤作用，包括 GC。然而，姜黄素是否通过调节铁死亡参与 GC 肿瘤发生尚不清楚。用姜黄素（0、10 和 20 μM）处理胃癌细胞 AGS 和 HGC-27。通过 CCK-8 和 LDH 释放测定评估细胞活力和死亡。通过免疫荧光染色评估细胞中 LC3B 的表达。通过相应的测定试剂盒评估细胞内亚铁离子（Fe2+）、GSH、MDA 和脂质 ROS 水平。通过 Western blot 测定细胞自噬标志物（ATG5、ATG7、Beclin 1 和 LC3B）、铁死亡标志物（ACSL4、SLC7A11 和 GPX4）和磷酸化（p）-PI3K、p-AKT 和 p-mTOR 的细胞水平。姜黄素减弱了 GC 细胞的活力，但刺激了其死亡。姜黄素增强了 GC 细胞中的自噬，表现为 ATG5、ATG7、Beclin 1 和 LC3B 的水平增加。此外，姜黄素上调铁、MDA、GSH 和 ACSL4 水平，同时下调脂质 ROS、SLC7A11 和 GPX4 水平，表明其刺激 GC 细胞发生铁死亡。姜黄素降低了细胞中 p-PI3K、p-AKT 和 p-mTOR 的水平。重要的是，铁死亡抑制剂 ferrostatin-1 逆转了姜黄素对 GC 细胞活力、死亡和铁死亡的影响。姜黄素通过抑制 PI3K/AKT/mTOR 信号通路激活诱导自噬介导的铁死亡来抑制 GC 的发展。
