Zhou Li, Xu Bin, Li Baojian
Department of Traditional Chinese Medicine, Changzhou Fourth People's Hospital, Changzhou City, Jiangsu Province, 213032, China.
Department of Pharmacy, The Fourth People's Hospital of Changzhou, No.68, Honghe Road, Xinbei District, Changzhou City, Jiangsu Province, 213032, China.
Hereditas. 2025 Jul 23;162(1):139. doi: 10.1186/s41065-025-00508-2.
Gastric cancer (GC) remains a significant global health challenge due to its high mortality and frequent resistance to chemotherapy drugs like cisplatin (DDP). Carnosic acid (CA), a phenolic diterpene, exhibits potential anti-cancer properties. This study aimed to investigate the role of CA in regulating GC development and DDP sensitivity.
The half-maximal inhibitory concentration (IC) of DDP and cell viability were determined using a cell counting kit-8 assay. Cell proliferation was evaluated by a 5-Ethynyl-2'-deoxyuridine assay, while cell migration was assessed by a transwell assay. Cell death was analyzed through flow cytometry, fluorometric assay, and colorimetric assays. The targets of CA were identified using network pharmacology. Western blotting was employed to detect the protein expression of tumor protein p53 (TP53), solute carrier family 7 member 11 (SLC7A11), and arachidonate 12-lipoxygenase, 12 S type (ALOX12).
CA treatment significantly inhibited GC cell proliferation and migration and enhanced cell death. The treatment also elevated reactive oxygen species (ROS) and Fe levels, while reducing glutathione (GSH) levels and the IC value for DDP in GC cells. In addition, TP53 was identified as a target of CA, and its protein expression was upregulated by CA treatment in GC cells. Silencing TP53 attenuated the effects of CA on cell proliferation, migration, death, and the sensitivity of tumor cells to DDP. Further, CA regulated the TP53-mediated SLC7A11/ALOX12 pathway.
CA improved the sensitivity of GC cells to DDP and inhibited their malignant progression by regulating the TP53-mediated SLC7A11/ALOX12 axis, highlighting its potential clinical significance for GC treatment.
由于胃癌（GC）死亡率高且对顺铂（DDP）等化疗药物频繁耐药，它仍然是一项重大的全球健康挑战。肌醇六磷酸（CA）是一种酚类二萜，具有潜在的抗癌特性。本研究旨在探讨CA在调节GC发展和DDP敏感性中的作用。
使用细胞计数试剂盒-8法测定DDP的半数最大抑制浓度（IC）和细胞活力。通过5-乙炔基-2'-脱氧尿苷法评估细胞增殖，同时通过Transwell法评估细胞迁移。通过流式细胞术、荧光测定法和比色测定法分析细胞死亡情况。使用网络药理学鉴定CA的靶点。采用蛋白质印迹法检测肿瘤蛋白p53（TP53）、溶质载体家族7成员11（SLC7A11）和12-S型花生四烯酸12-脂氧合酶（ALOX12）的蛋白表达。
CA处理显著抑制GC细胞增殖和迁移，并增强细胞死亡。该处理还提高了活性氧（ROS）和铁水平，同时降低了GC细胞中的谷胱甘肽（GSH）水平和DDP的IC值。此外，TP53被鉴定为CA的靶点，CA处理可上调GC细胞中其蛋白表达。沉默TP53可减弱CA对细胞增殖、迁移、死亡以及肿瘤细胞对DDP敏感性的影响。此外，CA调节TP53介导的SLC7A11/ALOX12途径。
CA通过调节TP53介导的SLC7A11/ALOX12轴提高了GC细胞对DDP的敏感性，并抑制了其恶性进展，突出了其在GC治疗中的潜在临床意义。
