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

Wang,Xuan; Jia,Lili; Jin,Xiaohua; Liu,Qian; Cao,Wei; Gao,Xiangdong; Yang,Mingfeng; Sun,Baoliang

doi:10.3892/ol.2015.3130

June-2015 Volume 9 Issue 6

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June-2015 Volume 9 Issue 6

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Article

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 / Copyright

Affiliations: Department of Neurology, The Sixth People's Hospital of Jinan, Jinan, Shandong 250200, P.R. China, Key Laboratory of Cerebral Microcirculation Taishan Medical University, Tai'an, Shangdong 271000, P.R. China
Pages: 2586-2590
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Published online on: April 21, 2015

https://doi.org/10.3892/ol.2015.3130
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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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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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