NMDA receptor signaling induces the chemoresistance of temozolomide via upregulation of MGMT expression in glioblastoma cells

Activation of N-methyl-D-aspartate receptors (NMDAR) elevated MGMT expression and suppressed the effect of temozolomide (TMZ) in glioblastoma cells.

• NMDAR signaling is associated with increased expression of MGMT, a DNA repair enzyme linked to TMZ resistance.
• Knockdown of NMDAR decreased MGMT expression, enhancing the effectiveness of TMZ in T98G cells.
• The combination of TMZ with memantine (MEM), an NMDAR antagonist, increased the cytotoxicity of TMZ.
• Inhibition of NMDAR by MEM resulted in reduced MGMT expression and increased DNA alkylation by TMZ.
• NMDAR signaling may play a crucial role in the chemoresistance of glioblastoma to TMZ.

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