Baicalein enhances radiosensitivity in cervical cancer by targeting ALOX15 and regulating lipid metabolism

Radiotherapy is the mainstay for locally advanced cervical cancer, but its efficacy is compromised by radioresistance. Dysregulated lipid metabolism contributes to therapeutic resistance, offering a promising strategy to improve radiosensitivity. This study aimed to explore the effect and mechanism of baicalein in enhancing radiosensitivity of cervical cancer cells. In vitro experiments were performed to assess the radiosensitizing effect of baicalein, while potential targets were identified through bioinformatics and network pharmacology. The key target was further validated by gene knockdown, and in vivo experiments were conducted to confirm the effects of baicalein combined with radiotherapy. ALOX15 was identified as a key target of baicalein, and high ALOX15 expression was associated with poor prognosis in cervical cancer. Both baicalein treatment and ALOX15 suppression enhanced radiosensitivity, reduced lipid droplet accumulation, and downregulated the SREBP1/FASN/ACC protein expression. In vivo, baicalein combined with radiotherapy reduced lipid accumulation and serum lipid levels, with effects comparable to those of the ALOX15 inhibitor AA861. Collectively, these findings suggest that baicalein enhances radiosensitivity in cervical cancer by targeting ALOX15 and modulating lipid metabolism via the SREBP1/FASN/ACC pathway. ALOX15 may be a potential regulator of radioresistance, and baicalein warrants further investigation as a potential radiosensitizer.