title: NF-κB inhibitor reverses temozolomide resistance in human glioma TR/U251 cells.
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 TMZin 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.
authors.affiliation: Department of Neurology, The Sixth People's Hospital of Jinan, Jinan, Shandong 250200, P.R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Sixth People's Hospital of Jinan, Jinan, Shandong 250200, P.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Neurology, The Sixth People's Hospital of Jinan, Jinan, Shandong 250200, P.R. China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Neurology, The Sixth People's Hospital of Jinan, Jinan, Shandong 250200, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Sixth People's Hospital of Jinan, Jinan, Shandong 250200, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Neurology, The Sixth People's Hospital of Jinan, Jinan, Shandong 250200, P.R. China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Gao
authors.affiliation: Key Laboratory of Cerebral Microcirculation Taishan Medical University, Tai'an, Shangdong 271000, P.R. China.
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Yang
authors.affiliation: Key Laboratory of Cerebral Microcirculation Taishan Medical University, Tai'an, Shangdong 271000, P.R. China.
authors.forename: Baoliang
authors.initials: B
authors.lastname: Sun
keywords: O6-methylguanine-DNA methyltransferase; glioblastoma multiforme; nuclear factor-κB