Dexmedetomidine promotes ferroptotic cell death in gastric cancer via hsa_circ_0008035/miR‐302a/E2F7 axis

Abstract

AbstractDexmedetomidine (DEX), a common anesthetic, has significant effects on the biological features of cancer cells. Although numerous studies have been published on the impact of DEX on the biological characteristics of GC cells, the mechanism remains unknown. This study aimed to explore the effect of DEX on the biological properties of GC cells. DEX suppressed the viability and increased the apoptosis of GC cells in vitro and inhibited tumor growth in vivo. Besides, DEX raised the levels of reactive oxygen species (ROS) and iron, but decreased the levels of glutathione (GSH), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11) in GC cells, which were abolished by Ferrostatin‐1 (the inhibitor of ferroptosis) treatment. In addition, the level of circ0008035 and E2F7 were downregulated, but miR‐302a level was upregulated in DEX‐treated GC cells. Circ0008035 increased the expression of E2F2 by acting as a sponge for miR‐302a. Circ0008035 inhibited DEX‐induced ferroptotic cell death in GC cells, which was reversed by miR‐302a overexpression or E2F7 reduction. Taken together, DEX mediated ferroptotic cell death in GC through regulating the circ0008035/miR‐302a/E2F7 axis, suggesting a feasible therapy option for GC.