VPA and MEL induce apoptosis by inhibiting the Nrf2-ARE signaling pathway in TMZ-resistant U251 cells

  • Authors:
    • Hao Pan
    • Handong Wang
    • Yue Jia
    • Qiang Wang
    • Liwen Li
    • Qi Wu
    • Longbang Chen
  • View Affiliations

  • Published online on: May 25, 2017     https://doi.org/10.3892/mmr.2017.6621
  • Pages: 908-914
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Abstract

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.
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July-2017
Volume 16 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Pan H, Wang H, Jia Y, Wang Q, Li L, Wu Q and Chen L: VPA and MEL induce apoptosis by inhibiting the Nrf2-ARE signaling pathway in TMZ-resistant U251 cells. Mol Med Rep 16: 908-914, 2017
APA
Pan, H., Wang, H., Jia, Y., Wang, Q., Li, L., Wu, Q., & Chen, L. (2017). VPA and MEL induce apoptosis by inhibiting the Nrf2-ARE signaling pathway in TMZ-resistant U251 cells. Molecular Medicine Reports, 16, 908-914. https://doi.org/10.3892/mmr.2017.6621
MLA
Pan, H., Wang, H., Jia, Y., Wang, Q., Li, L., Wu, Q., Chen, L."VPA and MEL induce apoptosis by inhibiting the Nrf2-ARE signaling pathway in TMZ-resistant U251 cells". Molecular Medicine Reports 16.1 (2017): 908-914.
Chicago
Pan, H., Wang, H., Jia, Y., Wang, Q., Li, L., Wu, Q., Chen, L."VPA and MEL induce apoptosis by inhibiting the Nrf2-ARE signaling pathway in TMZ-resistant U251 cells". Molecular Medicine Reports 16, no. 1 (2017): 908-914. https://doi.org/10.3892/mmr.2017.6621