ArticleJournal of neuro-oncology2022
NMDA receptor signaling induces the chemoresistance of temozolomide via upregulation of MGMT expression in glioblastoma cells.
Article in Journal of neuro-oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 9 citations in OpenAlex.
- Label-Free Raman Spectroscopy Reveals Metabolic Signatures Associated with MGMT Promoter Methylation Status in Glioblastoma.Analytical chemistry · 2026Article
- Glutamate Drives Glioblastoma Invasion in Three-Dimensional Hyaluronic Acid Hydrogels.Tissue engineering. Part A · 2026Article
- Synergistic antitumor and radiosensitizing effects of α-sulfoquinovosyl-acylpropanediol (SQAP) via PI3K/Akt inhibition and DNA repair impairment in glioblastoma.Journal of neuro-oncology · 2025Article
- A glutamatergic biomarker panel enables differentiating Grade 4 gliomas/astrocytomas from brain metastases.Frontiers in oncology · 2024Article
- Deciphering the CNS-glioma dialogue: Advanced insights into CNS-glioma communication pathways and their therapeutic potential.Journal of central nervous system disease · 2024Review
- Association ofInternational journal of molecular sciences · 2023Article
- The strange Microenvironment of Glioblastoma.Revue neurologique · 2023Review
- Epigenetics and Metabolism Reprogramming Interplay into Glioblastoma: Novel Insights on Immunosuppressive Mechanisms.Antioxidants (Basel, Switzerland) · 2023Review
- The Role of Hyperexcitability in Gliomagenesis.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe alkylating agent temozolomide (TMZ) has a significant impact on the prognosis of glioblastoma (GBM) patients. Therefore, maximizing TMZ efficacy is important for GBM treatment. Many reports have shown that glutamate signaling promotes GBM progression via glutamate receptors, including N-methyl-D-aspartate receptors (NMDARs). Although NMDARs promote cell migration and invasion of GBM cells, their role in TMZ resistance remains unclear. Therefore, we focused on NMDAR signaling and investigated its effects on TMZ resistance.
methodsWe investigated the effect of NMDAR signaling on O
resultsActivation of NMDAR by N-methyl-D-aspartate (NMDA) elevated MGMT expression and suppressed the effect of TMZ in T98G cells. In contrast, knockdown of NMDAR by NMDAR1 shRNA decreased MGMT expression and enhanced the effect of TMZ in T98G cells. The cytotoxic effect of TMZ was enhanced by MEM in T98G cells. Inhibition of NMDAR by MEM decreased MGMT expression and increased DNA alkylation by TMZ.
conclusionNMDAR signaling induced chemoresistance of TMZ via the upregulation of MGMT expression in GBM cells. Furthermore, MEM inhibited TMZ-induced MGMT upregulation and increased the cytotoxic effect of TMZ on MGMT-positive cells. This study demonstrates that the combination of TMZ and MEM could be a new therapeutic strategy for MGMT-positive GBM. Overview of this study. NMDAR signaling controls the expression of MGMT and the cytotoxic effect of TMZ.
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