NF-κB inhibitor reverses temozolomide resistance in human glioma TR/U251 cells

  • Authors:
    • Xuan Wang
    • Lili Jia
    • Xiaohua Jin
    • Qian Liu
    • Wei Cao
    • Xiangdong Gao
    • Mingfeng Yang
    • Baoliang Sun
  • View Affiliations

  • Published online on: April 21, 2015     https://doi.org/10.3892/ol.2015.3130
  • Pages: 2586-2590
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Abstract

Glioblastoma multiforme (GBM) demonstrates an unsatisfactory clinical prognosis due to the intrinsic or acquired resistance to temozolomide (TMZ) exhibited by the tumors. One possible cause of TMZ resistance in GBM is the overexpression of O6‑methylguanine‑DNA methyltransferase (MGMT), which can repair the TMZ‑induced guanine damage in DNA. Additionally, excessive activated NF‑κB is reported to be a component of the major inflammatory transcription pathway that is associated with TMZ resistance in GBM. However, the association between the NF‑κB pathway and MGMT expression in GBM cells is unknown. Therefore, in the present study, the TMZ resistant (TR) U251 cell line (TR/U251) was successfully constructed to detect how the TR/U251 cell line and the parental U251 cell line each interact with TMZ in vitro. The TR/U251 cells were approximately five times more resistant to TMZ compared with the parental cells. Furthermore, it was found that the NF‑κB inhibitor BAY 11‑7082 suppressed the expression of MGMT in TR/U251 cells and enhanced TMZ‑induced cytotoxicity and apoptosis, thereby indicating that the NF‑κB pathway and MGMT interact to promote TMZ resistance. The inhibition of NF‑κB may be a promising strategy to reverse drug resistance in TR glioma cells. The present results propose a potential mechanism for using the NF‑κB inhibitor BAY 11‑7082 as a potential therapy for the treatment of TR glioma. Although BAY 11‑7082 is a well‑known NF‑ κB inhibitor, the present study further investigated its underlying mechanisms through a series of new experiments.
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June-2015
Volume 9 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Wang X, Jia L, Jin X, Liu Q, Cao W, Gao X, Yang M and Sun B: NF-κB inhibitor reverses temozolomide resistance in human glioma TR/U251 cells. Oncol Lett 9: 2586-2590, 2015
APA
Wang, X., Jia, L., Jin, X., Liu, Q., Cao, W., Gao, X. ... Sun, B. (2015). NF-κB inhibitor reverses temozolomide resistance in human glioma TR/U251 cells. Oncology Letters, 9, 2586-2590. https://doi.org/10.3892/ol.2015.3130
MLA
Wang, X., Jia, L., Jin, X., Liu, Q., Cao, W., Gao, X., Yang, M., Sun, B."NF-κB inhibitor reverses temozolomide resistance in human glioma TR/U251 cells". Oncology Letters 9.6 (2015): 2586-2590.
Chicago
Wang, X., Jia, L., Jin, X., Liu, Q., Cao, W., Gao, X., Yang, M., Sun, B."NF-κB inhibitor reverses temozolomide resistance in human glioma TR/U251 cells". Oncology Letters 9, no. 6 (2015): 2586-2590. https://doi.org/10.3892/ol.2015.3130