NDLI: IDH1 R132H mutation regulates glioma chemosensitivity through Nrf2 pathway

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IDH1 R132H mutation regulates glioma chemosensitivity through Nrf2 pathway

Content Provider	Semantic Scholar
Author	Li, Kaishu Ouyang, Leping He, Mingliang Luo, Ming Cai, Wangqing Tu, Yalin Pi, Rongbiao Liu, Anmin
Copyright Year	2017
Abstract	PURPOSE Numerous 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. METHODS Wild 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. RESULTS The 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. CONCLUSIONS Nrf2 played an important role in IDH1 R132H-mediated drug resistance. The present study provides new insight for glioma chemotherapy with temozolomide.
Starting Page	28865
Ending Page	28879
Page Count	15
File Format	PDF HTM / HTML
DOI	10.18632/oncotarget.15868
PubMed reference number	28427200
Journal	Medline
Volume Number	8
Alternate Webpage(s)	http://www.oncotarget.com/index.php?journal=oncotarget&op=download&page=article&path%5B%5D=15868&path%5B%5D=54113
Alternate Webpage(s)	https://doi.org/10.18632/oncotarget.15868
Journal	Oncotarget
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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