Ferroptosis Targeting by β-Sitosterol in Cervical Cancer Radiotherapy

This review addresses the challenge of radioresistance in cervical cancer by exploring the role of ferroptosis in enhancing the efficacy of radiotherapy (RT). It emphasizes the radiosensitizing effect of β-sitosterol through modulation of the GPX4/ACSL4 axis. β-Sitosterol targets mitochondrial membranes, inhibits GPX4 activity, and activates ACSL4, promoting polyunsaturated fatty acid synthesis and thereby facilitating ferroptosis. Preclinical models demonstrate that β-sitosterol significantly improves RT sensitivity and increases tumor iron accumulation. The review further proposes a predictive framework based on ox-LDL levels and the ACSL4/GPX4 ratio for potential clinical application, alongside discussions on innovative delivery systems, ferroptosis-apoptosis interactions, microbiota-mediated metabolic effects, and AI-driven optimization of RT-- drug combinations. These insights contribute to advancing personalized radiotherapy strategies for cervical cancer.