TRAIL predisposes non-small cell lung cancer to ferroptosis by regulating ASK-1/JNK1 pathway
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View abstract on PubMed
Summary
This summary is machine-generated.Overexpressing TNF-related apoptosis-inducing ligand (TRAIL) triggers ferroptosis in non-small cell lung cancer (NSCLC) cells, inhibiting tumor growth. This occurs via the ASK-1/JNK1 pathway, offering potential new NSCLC therapies.
Area Of Science
- Oncology
- Molecular Biology
- Cancer Research
Background
- Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality.
- The role of TNF-related apoptosis-inducing ligand (TRAIL) and its interplay with ferroptosis in NSCLC is not fully understood.
- Identifying novel therapeutic targets and mechanisms is crucial for improving NSCLC treatment outcomes.
Purpose Of The Study
- To investigate the relationship between TRAIL expression and ferroptosis in NSCLC development.
- To elucidate the molecular mechanisms by which TRAIL influences ferroptosis in NSCLC cells.
- To evaluate the therapeutic potential of TRAIL in NSCLC models.
Main Methods
- TRAIL expression was quantified using western blot, RT-qPCR, and immunohistochemistry.
- Cell viability, migration, and invasion were assessed using CCK-8, wound healing, and Transwell assays.
- Ferroptosis markers, including labile iron pool (LIP), iron levels, ferrous iron (Fe<sup>2+</sup>), lipid peroxidation, and antioxidant enzymes (SOD, CAT, MDA), were measured. In vivo studies utilized mouse tumor xenograft models.
Main Results
- TRAIL expression was significantly reduced in NSCLC cell lines (H1299, NCL-H1395, A549) compared to normal cells (BEAS-2B).
- Upregulating TRAIL expression decreased NSCLC cell viability, migration, and invasion, while promoting ferroptosis by increasing LIP, iron, Fe<sup>2+</sup>, and lipid peroxidation, and reducing ferroptosis suppressors (FTH1, GPX4, SLC7A11).
- TRAIL activated the ASK-1/JNK1 pathway, and inhibition of ASK-1 attenuated TRAIL's anti-tumor and ferroptosis-inducing effects. TRAIL suppressed tumor growth and ferroptosis in vivo.
Conclusions
- Overexpression of TRAIL induces ferroptosis in NSCLC cells, leading to significant anti-tumor effects.
- The mechanism involves the activation of the ASK-1/JNK1 pathway, mediating TRAIL-induced ferroptosis.
- These findings suggest TRAIL as a promising therapeutic strategy for NSCLC treatment.
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