Abstract
Gliomas, the most prevalent primary brain tumors, exhibit a poor five-year survival rate despite advances in various treatments, necessitating further studies to understand tumor progression and develop new therapies, particularly targeting EphA2, which is implicated in vasculogenic mimicry and glioma progression. Dihydroartemisinin (DHA) has shown anti-glioma effects through mechanisms such as PERK-related ferroptosis and inhibition of proliferation and angiogenesis, although its interaction with EphA2 in mediating these effects requires further investigation. In this study, we revealed that DHA significantly inhibits the formation of vasculogenic-like networks, the stemness of C6 glioma stem cells and the growth of glioma by inhibiting the expression of EphA2. Mechanistic investigations indicated that PI3K/Akt pathway at least partly mediated this function, since overexpression of EphA2 reversed the anti-tumor effects of DHA. Conclusively, the current report provides evidence that DHA, PI3K/Akt/EphA2 blockage, and VM inhibition are promising therapies for glioma.