Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, and radiotherapy is a common treatment for NSCLC; however, it is often hampered by drug and radiation resistance. Magnolol is a polyphenol compound extracted from Magnolia officinalis bark and has multiple biological activities. Nevertheless, its specific role and mechanism in enhancing the effect of radiotherapy for NSCLC remain unclear. This study aimed to explore the synergistic effect of magnolol combined with radiotherapy in non-small cell lung cancer and its mechanism.

CL1-5-F4 and HCC827 were treated with 15 µM magnolol and a radiation dose of 4 Gy. Cell viability was assessed using the MTT assay, while proliferation ability was evaluated through colony formation assays. Apoptosis and DNA damage repair were analyzed using flow cytometry. Additionally, Western blotting was employed to detect the expression of apoptosis-related proteins.

MTT assays demonstrated that magnolol inhibited NSCLC cell proliferation, with 15 µM reducing cell viability . Colony formation assays revealed that the combination of magnolol and 4 Gy radiation significantly reduced colony formation compared to single treatments. Apoptosis analysis confirmed enhanced activation of caspase-3, -8, and -9, indicating the induction of both intrinsic and extrinsic apoptotic pathways. Annexin V staining showed increased early and late apoptosis in the combined treatment group. Elevated mitochondrial membrane potential loss suggested that magnolol exacerbates radiation-induced damage through mitochondrial dysfunction. Furthermore, magnolol modulated the ATM-CHK2 pathway, enhancing sensitivity to DNA damage. Western blot analysis revealed increased expression of pro-apoptotic proteins (BIM, BAK, BAX, and BID) in the combined treatment group. These findings indicate that magnolol enhances radiotherapy efficacy by promoting apoptosis and disrupting DNA repair, offering a promising strategy for NSCLC treatment.

Magnolol significantly enhances the sensitivity of NSCLC cells to radiotherapy. Its mechanisms likely involve the inhibition of DNA damage repair and induction of apoptosis .These results provide strong evidence supporting the potential of magnolol as a radiosensitizer in NSCLC treatment.