Yang Chang, Xue Rui, Qin Chuling, Huang Lingyue, Nie Rongrong, Luo Yuqin, Xu Siyuan, Tang Ke, Chen Jianning, Jia Lulu, Tan Qinyou
Department of Clinical Pharmacy, School of Pharmacy, Guilin Medical University, Guilin 541001, Guangxi, China.
Clinical Pharmacy & Pharmacology Research Institute, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi, China.
Am J Chin Med. 2025;53(3):931-949. doi: 10.1142/S0192415X25500351.
Gastric cancer is a significant global health issue. Celastrol, a natural compound, has shown antitumor potential, but its molecular mechanism in gastric cancer remains unclear. In this study, we treated HGC-27 cells with celastrol and employed CCK8, colony formation, and Transwell assays, revealing its inhibitory effect on cell proliferation and migration. Flow cytometry assay results showed that celastrol could elevate the level of reactive oxygen species (ROS) in HGC-27 cells. By using the iron ion and malondialdehyde (MDA) detection kits, it was found that celastrol promoted the accumulation of iron ions (Fe[Formula: see text] in HGC-27 cells, increased the MDA content, and simultaneously decreased the glutathione (GSH) content. Additionally, Western blot analysis indicated that celastrol exerts an inhibitory effect on the expression of ferroptosis-marker proteins GPX4 and SLC7A11. PCR array and further experiments identified CERKL as a key factor, whose downregulation by celastrol was associated with enhanced ferroptosis. , celastrol inhibited tumor growth without affecting body weight or organ histology. Our findings suggest that celastrol may inhibit gastric cancer via CERKL-regulated ferroptosis, providing a potential therapeutic strategy.
胃癌是一个重大的全球健康问题。雷公藤红素是一种天然化合物，已显示出抗肿瘤潜力，但其在胃癌中的分子机制仍不清楚。在本研究中，我们用雷公藤红素处理HGC - 27细胞，并采用CCK8、集落形成和Transwell实验，揭示了其对细胞增殖和迁移的抑制作用。流式细胞术检测结果表明，雷公藤红素可提高HGC - 27细胞中的活性氧（ROS）水平。通过使用铁离子和丙二醛（MDA）检测试剂盒，发现雷公藤红素促进HGC - 27细胞中铁离子（Fe[化学式：见原文]）的积累，增加MDA含量，同时降低谷胱甘肽（GSH）含量。此外，蛋白质印迹分析表明，雷公藤红素对铁死亡标记蛋白GPX4和SLC7A11的表达具有抑制作用。PCR阵列和进一步实验确定CERKL是一个关键因素，雷公藤红素对其下调与增强铁死亡有关。此外，雷公藤红素抑制肿瘤生长而不影响体重或器官组织学。我们的研究结果表明，雷公藤红素可能通过CERKL调节的铁死亡抑制胃癌，提供了一种潜在的治疗策略。
