Disruption of NF-κB signaling by fluoxetine attenuates MGMT expression in glioma cells

OncoTargets and Therapy
Tao SongYong Guo

Abstract

Resistance to temozolomide (TMZ) in glioma is modulated by the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). This study aimed to examine the effects of fluoxetine (FLT) on MGMT expression in glioma cells and to investigate its underlying mechanisms. Expression of MGMT, GluR1, or IκB kinase β (IKKβ) was attenuated using short hairpin RNA-mediated gene knockdown. The 3-(4,5-dimethylthiazol -2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the growth inhibition induced by FLT or TMZ. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) was conducted to detect apoptotic cells. Western blotting was conducted to analyze the protein expression of MGMT, IKKβ, and NF-κB/p65 following FLT treatment. The murine subcutaneous xenograft model was used to evaluate the combinational effect of TMZ and FLT. FLT markedly reduced MGMT expression in glioma cells, which was independent of GluR1 receptor function. Further, FLT disrupted NF-κB/p65 signaling in glioma cells and consequently attenuated NF-κB/p65 activity in regulating MGMT expression. Importantly, FLT sensitized MGMT-expressing glioma cells to TMZ, as FLT enhanced TMZ's ability to impair the in vitro tumorige...Continue Reading

Citations

Jan 14, 2018·Journal of Cellular Biochemistry·Zhikuan YangJihong Zhang
Mar 11, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Justin Fortune CreedenCheryl B McCullumsmith

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Methods Mentioned

BETA
PCR
xenografts
xenograft
transfection

Software Mentioned

Calcusyn

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