Baicalin induces ferroptosis in cervical squamous cell carcinoma via the NRF2/SLC7A11/GPX4 signaling axis

OBJECTIVE: To explore whether baicalin induces ferroptosis in cervical squamous cell carcinoma (CSCC) via regulating the NRF2/SLC7A11/GPX4 axis, thereby inhibiting CSCC progression. METHODS: ) and cell viability. Transmission electron microscopy (TEM) observed mitochondrial morphology; flow cytometry detected intracellular reactive oxygen species (ROS); kits measured malondialdehyde (MDA) and glutathione (GSH). Quantitative real-time PCR (qPCR) and Western blot analyzed NRF2/SLC7A11/GPX4 expression. In vivo, tumor vol/wt, HE staining (pathology), Prussian blue (iron deposition), and immunohistochemistry (IHC for target proteins) were evaluated. RESULTS: 48.12 μg/mL (SiHa) and 31.87 μg/mL (Caski) at 24 h. TEM showed ferroptotic mitochondrial changes (shrinkage, cristae loss, increased membrane density) in baicalin-treated cells. Baicalin elevated ROS (P < 0.001) and MDA (P < 0.01), reduced GSH (P < 0.05), and downregulated NRF2/SLC7A11/GPX4 mRNA/protein (P < 0.05) in CSCC cells. NRF2 overexpression reversed these baicalin-induced changes (P < 0.01). In vivo, baicalin reduced tumor vol/wt (P < 0.05), induced tumor necrosis, increased iron deposition (P < 0.001), and downregulated NRF2/SLC7A11/GPX4 in tumor tissues (P < 0.05). CONCLUSION: Baicalin induces ferroptosis in CSCC by inhibiting the NRF2/SLC7A11/GPX4 axis, suppressing CSCC progression. This provides experimental basis for baicalin as a potential targeted agent against CSCC.