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Nitroxoline Enhances Radiosensitivity in Non-Small Cell Lung Cancer by Suppressing STAT3-AKT-MTOR Survival Signaling
Eun-Young Gong1, Hye Won Lee1, Hyunseung Oh2
1Department of Pathology, Keimyung University School of Medicine, Daegu 1095, Republic of Korea.
International Journal of Molecular Sciences
|March 14, 2026
Summary
Nitroxoline, an antimicrobial drug, enhances non-small cell lung cancer (NSCLC) radiosensitivity by inhibiting STAT3 signaling. This combination therapy boosts cancer cell death and DNA damage, improving radiotherapy effectiveness.
Area of Science:
- Oncology
- Radiotherapy
- Molecular Biology
Background:
- Radiotherapy is crucial for non-small cell lung cancer (NSCLC) treatment.
- Cancer cells develop resistance to radiation through survival signaling pathways.
- STAT3 is a key regulator of cellular survival post-radiation exposure.
Purpose of the Study:
- To investigate if nitroxoline, a STAT3 inhibitor, can enhance radiosensitivity in NSCLC cells.
- To elucidate the mechanisms by which nitroxoline affects NSCLC radiosensitivity.
Main Methods:
- Examined the combined effects of nitroxoline and radiation on NSCLC cell viability.
- Analyzed key signaling pathways (STAT3, AKT, mTOR) and apoptosis markers (p53, PARP, caspase-3).
- Assessed DNA damage response markers (γ-H2AX, DNA-PKcs).
Main Results:
- Nitroxoline significantly increased radiation-induced cytotoxicity and reduced NSCLC cell survival.
- Nitroxoline suppressed basal and radiation-induced phosphorylation of STAT3, AKT, and mTOR.
- The combination therapy enhanced apoptosis and amplified radiation-induced DNA damage.
Conclusions:
- Nitroxoline acts as a radiosensitizer in NSCLC by inhibiting the STAT3-AKT-mTOR pathway.
- This suppression promotes apoptosis and enhances DNA damage, improving radiotherapy outcomes.
- Repurposing nitroxoline shows potential for enhancing NSCLC treatment effectiveness.
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