Effect of Feiyanning Granules on Inducing Ferroptosis in Lung Cancer Cells and Its Regulatory Function onNrf2/SLC7A11/GPX4 Signaling Pathway
10.13422/j.cnki.syfjx.20250824
- VernacularTitle:肺岩宁颗粒诱导肺癌细胞铁死亡及对Nrf2/SLC7A11/GPX4信号通路的影响
- Author:
Xin LIU
1
;
Wenjie WANG
1
;
Zhenye XU
1
;
Zhan ZHENG
1
Author Information
1. Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032,China
- Publication Type:Journal Article
- Keywords:
Feiyanning granule;
lung cancer;
ferroptosis;
nuclear transcription factor E2-related factor 2 (Nrf2)/mouse solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway;
traditional Chinese medicine
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(2):100-107
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveThis study aims to explore the effect of Feiyanning granules on ferroptosis in lung cancer cells and its regulatory function within the nuclear transcription factor E2-related factor 2 (Nrf2)/mouse solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway. MethodsThe cell counting kit-8 (CCK-8) method was used to detect the effect of Feiyanning granule on the proliferation of A549 lung cancer cells. A549 lung cancer cells were categorized into a blank group, a ferroptosis inhibitor-1 (Fer-1) group (10 μmol·L-1), a Feiyanning granules (600 mg·L-1) group, and a Feiyanning granules + Fer-1 group. After 48 hours of intervention, the activity and morphology of the cells were observed. The CCK-8 method was employed to measure cell viability. Biochemical assays were carried out to measure the levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and ferrous ions (Fe²⁺) in A549 cells. Western blot was utilized to evaluate the expression levels of Kelch-like ECH-associated protein 1 (Keap1), Nrf2, SLC7A11, and GPX4 proteins. A549 lung cancer cells were categorized into a blank group and a Feiyanning Granule group (600 mg·L-1), and mitochondrial morphology was examined via transmission electron microscopy (TEM). ResultsAfter the intervention of Feiyaning granules, the proliferation of A549 cells was significantly inhibited in a concentration-dependent manner compared with that in the blank group (P<0.01). Compared with the blank group, the Feiyanning granules group exerted an significantly inhibitory effect on the viability of lung cancer cells (P<0.01). Compared with that in the Feiyanning granules group, the cell viability in the Feiyanning granules +Fer-1 group was obviously restored (P<0.05). Compared with the blank group, the Feiyanning Granule group showed a significant increase in the levels of ROS, MDA, and Fe²⁺ (P<0.01), a significant decrease in the GSH level (P<0.01), and facilitated ferroptosis. Compared with the blank group, the Feiyanning granules group showed significantly decreased expression of Nrf2, SLC7A11, and GPX4 proteins and enhanced expression of Keap1 (P<0.01). Compared with those in the Feiyanning Granule group, the protein levels of Nrf2, SLC7A11, and GPX4 increased significantly (P<0.01), and the expression of Keap1 decreased significantly in the Feiyanning granules + Fer-1 group (P<0.01). Compared with the blank group, the Feiyaning granules group exhibited reduced mitochondrial size and increased matrix electron density. ConclusionFeiyanning granules can induce ferroptosis in lung cancer cells, and its underlying mechanism might be associated with the inhibition of the Nrf2/SLC7A11/GPX4 signaling pathway.