To investigate the induction of ferroptosis-related changes in osteosarcoma cells by lenvatinib and its effects on malignant behavior and molecular mechanisms.
Key Findings:
Lenvatinib inhibited the proliferation of 143B and U2OS cells in a concentration-dependent manner, suggesting a potential therapeutic window.
Ferroptosis-associated mitochondrial alterations were observed, including mitochondrial shrinkage and increased membrane density, indicating a shift in cellular metabolism.
Lenvatinib increased intracellular Fe2+, reactive oxygen species, and lipid peroxidation levels while decreasing reduced glutathione, highlighting its role in oxidative stress.
Lenvatinib treatment was associated with increased p53 expression and reduced xCT expression, linking it to tumor suppressor pathways.
Lenvatinib inhibited STAT3 phosphorylation, and ferrostatin-1 attenuated changes in p-STAT3 and p53, suggesting a feedback mechanism.
Interpretation:
Lenvatinib suppresses osteosarcoma cell proliferation, migration, and invasion by inducing ferroptosis-related changes, modulating the p-STAT3/p53/xCT axis, which may inform future therapeutic strategies.
Limitations:
The study primarily focused on specific osteosarcoma cell lines, which may not represent the heterogeneity of all osteosarcoma types.
Further investigation is needed to fully elucidate the clinical relevance of these findings, including in vivo studies.
Conclusion:
The study reveals a previously underrecognized mechanism of lenvatinib action, supporting further investigation of ferroptosis-targeted strategies in osteosarcoma to improve treatment outcomes.
