期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 954, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2023.175853
关键词
Isoorientin; Lung cancer; SIRT6; Nrf2; GPX4 pathway; ROS; Ferroptosis
Cisplatin is an effective chemotherapy drug, but drug resistance is a clinical concern. This study found that isoorientin can reverse drug resistance in lung cancer by promoting ferroptosis through the SIRT6/Nrf2/GPX4 signaling pathway, providing a theoretical basis for its potential clinical application.
Cisplatin, or DDP, is a highly successful and well-known chemotherapy drug used to treat cancer. Acquired resistance to chemotherapy is a major clinical concern, yet the mechanisms of this resistance are still unknown. Ferroptosis is a type of cell death distinct from other forms, fueled by a buildup of iron-associated lipid reactive oxygen species (ROS). Gaining insight into the process of ferroptosis could lead to novel treatments for overcoming cancer resistance. In this study, the combination of isoorientin (IO) and DDP treatment resulted in a significant decrease in the viability of drug-resistant cells, a substantial increase in intracellular iron, malondialdehyde (MDA) and ROS concentrations, a notable decrease in glutathione concentration, and the occurrence of ferroptosis in cells, as revealed by in vitro and in vivo experiments. Additionally, there was a decrease in the expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), and sirtuin 6 (SIRT6) proteins, and an increase in cellular ferroptosis. Isoorientin acts as a mediator to regulate cellular ferroptosis and reverse drug resistance in lung cancer cells by controlling the SIRT6/Nrf2/GPX4 signaling pathway. The findings of this study suggest that IO can promote ferroptosis and reverse drug resistance in lung cancer through the SIRT6/Nrf2/GPX4 signaling pathway, thus offering a theoretical basis for its potential clinical application.
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