VPA and MEL induce apoptosis by inhibiting the Nrf2-ARE signaling pathway in TMZ-resistant U251 cells.
In: Molecular Medicine Reports, Jg. 16 (2017-07-01), Heft 1, S. 908-914
academicJournal
Zugriff:
Chemoresistance is the primary obstacle to effective treatment of glioblastoma, the most lethal brain tumor. Our previous study demonstrated that Nf-E2 related factor 2 (Nrf2), a traditional cytoprotective transcription factor, was overexpressed in gliomas and promoted malignancy. The present study aimed to investigate the expression levels of Nrf2-antioxidant response element (ARE) signaling pathway genes in temozolomide (TMZ)-resistant U251 human glioblastoma cells (U251-TMZ). Additionally, the effect of valproic acid (VPA) and melatonin (MEL) on Nrf2 expression in U251-TMZ cells and their association with chemoresistance was investigated. The results of the present study indicated that the expression levels of components of the Nrf2-ARE signaling pathway were increased in U251-TMZ cells compared with U251 parent cells. Silencing of Nrf2 by transfection with small interfering RNA restored the chemosensitivity of U251-TMZ cells. The Nrf2 inhibitors VPA and MEL successfully reduced Nrf2 expression and survival in U251-TMZ cells treated with TMZ, accompanied by increased reactive oxygen species levels and apoptosis. Therefore, VPA and MEL may be potential chemotherapeutic sensitizers for the treatment of chemoresistant glioblastoma. [ABSTRACT FROM AUTHOR]
Titel: |
VPA and MEL induce apoptosis by inhibiting the Nrf2-ARE signaling pathway in TMZ-resistant U251 cells.
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Autor/in / Beteiligte Person: | Pan, Hao ; Wang, Handong ; Jia, Yue ; Wang, Qiang ; Li, Liwen ; Wu, Qi ; Chen, Longbang |
Zeitschrift: | Molecular Medicine Reports, Jg. 16 (2017-07-01), Heft 1, S. 908-914 |
Veröffentlichung: | 2017 |
Medientyp: | academicJournal |
ISSN: | 1791-2997 (print) |
DOI: | 10.3892/mmr.2017.6621 |
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