Carnosol enhances radiosensitivity in NSCLC cells by targeting the miR-17-5p/TOLLIP/NF-κB Axis.

Radioresistance limits the efficacy of radiotherapy in non-small cell lung cancer (NSCLC). This study investigates whether carnosol, a natural diterpene from rosemary, enhances NSCLC radiosensitivity by modulating the miR-17-5p/TOLLIP/NF-κB axis. A549 cells were treated with carnosol (30 μM) and X-ray irradiation (6 Gy). Cell viability, apoptosis, and DNA damage were evaluated by CCK-8, clonogenic, TUNEL, and comet assays. qRT-PCR, Western blotting, and dual-luciferase assays assessed pathway components and interactions. Carnosol downregulated miR-17-5p and upregulated TOLLIP, suppressing TLR4 and p-NF-κB p65 while increasing IκBα expression. These alterations impaired DNA repair (evidenced by increased γH2AX and decreased RAD51), enhanced radiation-induced apoptosis, and reduced clonogenic survival (all P < 0.01). miR-17-5p mimics partially reversed these effects. Carnosol may exert its radiosensitizing effect in NSCLC by targeting the miR-17-5p/TOLLIP/NF-κB axis and disrupting DNA repair, highlighting its therapeutic potential in overcoming radioresistance.