ArticleOncotarget2017
IDH1 R132H mutation regulates glioma chemosensitivity through Nrf2 pathway.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
- Reprogramming oncogenic mitochondria in pancreatic adenocarcinoma through BRD4 inhibition leads to programmed cell death.The Journal of pharmacology and experimental therapeutics · 2025Article
- Impact of NQO1 dysregulation in CNS disorders.Journal of translational medicine · 2024Review
- Implications of ConcurrentCurrent issues in molecular biology · 2022Article
- Characterization and comparison of human glioblastoma models.BMC cancer · 2022Article
- Normal and Pathological NRF2 Signalling in the Central Nervous System.Antioxidants (Basel, Switzerland) · 2022Review
- The Role of NRF2/KEAP1 Pathway in Glioblastoma: Pharmacological Implications.Medical oncology (Northwood, London, England) · 2022Review
- From Metabolism to Genetics and Vice Versa: The Rising Role of Oncometabolites in Cancer Development and Therapy.International journal of molecular sciences · 2021Review
- Review
- Metabolic Drivers of Invasion in Glioblastoma.Frontiers in cell and developmental biology · 2021Review
- PI3K/mTOR inhibition of IDH1 mutant glioma leads to reduced 2HG production that is associated with increased survival.Scientific reports · 2019Article
- Article
- Wild-type and mutated IDH1/2 enzymes and therapy responses.Oncogene · 2018Review
- Bioengineered NRF2-siRNA Is Effective to Interfere with NRF2 Pathways and Improve Chemosensitivity of Human Cancer Cells.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Cystathionine-γ-lyase drives antioxidant defense in cysteine-restricted IDH1-mutant astrocytomas.Neuro-oncology advancesArticle
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
purposeNumerous studies have reported that glioma patients with isocitrate dehydrogenase 1(IDH1) R132H mutation are sensitive to temozolomide treatment. However, the mechanism of IDH1 mutations on the chemosensitivity of glioma remains unclear. In this study, we investigated the role and the potential mechanism of Nrf2 in IDH1 R132H-mediated drug resistance.
methodsWild type IDH1 (R132H-WT) and mutant IDH1 (R132H) plasmids were constructed. Stable U87 cells and U251 cells overexpressing IDH1 were generated. Phenotypic differences between IDH1-WT and IDH1 R132H overexpressing cells were evaluated using MTT, cell colony formation assay, scratch test assay and flow cytometry. Expression of IDH1 and its associated targets, nuclear factor-erythroid 2-related factor 2 (Nrf2), NAD(P)H quinine oxidoreductase 1 (NQO1), multidrug resistant protein 1 (MRP1) and p53 were analyzed.
resultsThe IDH1 R132H overexpressing cells were more sensitive to temozolomide than WT and the control, and Nrf2 was significantly decreased in IDH1 R132H overexpressing cells. We found that knocking down Nrf2 could decrease resistance to temozolomide. The nuclear translocation of Nrf2 in IDH1 R132H overexpressing cells was lower than the WT and the control groups after temozolomide treatment. When compared with WT cells, NQO1 expression was reduced in IDH1 R132H cells, especially after temozolomide treatment. P53 was involved in the resistance mechanism of temozolomide mediated by Nrf2 and NQO1.
conclusionsNrf2 played an important role in IDH1 R132H-mediated drug resistance. The present study provides new insight for glioma chemotherapy with temozolomide.
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