Polystyrene Microplastics Induce Radiotherapy Resistance in Lung Cancer by Suppressing Ferroptosis Through NF-κB...

Area of Science:

• Oncology
• Environmental Science
• Cell Biology

Background:

• Polystyrene microplastics (PS-MPs) are environmental pollutants with unknown effects on cancer therapy.
• Ferroptosis and NF-κB pathways are critical in cancer progression and treatment response.

Purpose of the Study:

• To investigate the impact of PS-MPs on lung cancer radiotherapy efficacy.
• To elucidate the role of PS-MPs in ferroptosis regulation and NF-κB pathway activation in lung cancer.

Main Methods:

• Exposure of lung cancer cells and mice to PS-MPs.
• Assessment of cell proliferation, mitochondrial morphology, and ferroptosis markers.
• Transcriptomic analysis to identify pathway activation.
• NF-κB pathway manipulation (knockdown) to confirm mechanisms.
• Evaluation of tumor growth and survival rates in vivo.

Main Results:

• PS-MPs were internalized by lung cancer cells and promoted proliferation.
• PS-MPs attenuated radiation-induced ferroptosis by inhibiting lipid peroxidation and glutathione depletion.
• PS-MPs activated the NF-κB pathway, increasing its signaling components.
• In vivo studies showed PS-MPs reduced radiotherapy efficacy, increasing tumor burden and decreasing survival.
• NF-κB knockdown restored ferroptosis sensitivity and reversed PS-MPs-induced radioresistance.

Conclusions:

• PS-MPs impair lung cancer radiotherapy by suppressing ferroptosis via NF-κB activation.
• This study highlights the oncological impact of microplastics as environmental disruptors of redox homeostasis.
• Findings suggest microplastics may influence cancer therapy resistance, necessitating further research in environmental oncology.