Kaempferol regulates Ewing sarcoma progression via miR-26b-5p-mediated expression of the family with sequence similarity 98 member A.

Ewing sarcoma (ES) is a highly aggressive pediatric bone cancer with limited treatment options for metastatic or recurrent cases. This study investigated the antitumor effects of kaempferol, a natural flavonoid, on ES and its underlying molecular mechanisms. In vitro experiments demonstrated that kaempferol significantly inhibited the proliferation, migration, and invasion of SK-ES-1 cells in a dose- and time-dependent manner. Mechanistically, kaempferol upregulated miR-26b-5p, which directly targeted and suppressed FAM98A, a pro-oncogenic protein. This regulation led to the inhibition of the EGFR/PI3K/AKT/NF-κB signaling pathway, reducing tumor growth and metastasis. In vivo studies further confirmed that kaempferol suppressed ES tumor growth in a xenograft mouse model, while miR-26b-5p knockdown partially reversed this effect. Our findings suggest that kaempferol exerts its antitumor activity in ES by modulating the miR-26b-5p/FAM98A axis and downstream signaling pathways, highlighting its potential as a novel therapeutic agent for ES treatment.