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Celecoxib Suppresses NF-κB p65 (RelA) and TNFα Expression Signaling in Glioblastoma

Background: Glioblastoma (GBM) harbors significant genetic heterogeneity, high infiltrative capacity, and patterns of relapse following many therapies. The expression of nuclear factor kappa-B (NF-κB p65 (RelA)) and signaling pathways is constitutively activated in GBM through inflammatory stimulati...

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Autores principales: Ahsan, Hina, Malik, Shaukat Iqbal, Shah, Fawad Ali, El-Serehy, Hamed A., Ullah, Amin, Shah, Zafar Abbas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10607796/
https://www.ncbi.nlm.nih.gov/pubmed/37892820
http://dx.doi.org/10.3390/jcm12206683
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author Ahsan, Hina
Malik, Shaukat Iqbal
Shah, Fawad Ali
El-Serehy, Hamed A.
Ullah, Amin
Shah, Zafar Abbas
author_facet Ahsan, Hina
Malik, Shaukat Iqbal
Shah, Fawad Ali
El-Serehy, Hamed A.
Ullah, Amin
Shah, Zafar Abbas
author_sort Ahsan, Hina
collection PubMed
description Background: Glioblastoma (GBM) harbors significant genetic heterogeneity, high infiltrative capacity, and patterns of relapse following many therapies. The expression of nuclear factor kappa-B (NF-κB p65 (RelA)) and signaling pathways is constitutively activated in GBM through inflammatory stimulation such as tumor necrosis factor-alpha (TNFα), cell invasion, motility, abnormal physiological stimuli, and inducible chemoresistance. However, the underlying anti-tumor and anti-proliferative mechanisms of NF-κB p65 (RelA) and TNFα are still poorly defined. This study aimed to investigate the expression profiling of NF-κB p65 (RelA) and TNFα as well as the effectiveness of celecoxib along with temozolomide (TMZ) in reducing the growth of the human GBM cell line SF-767. Methods: genome-wide expression profiling, enrichment analysis, immune infiltration, quantitative expression, and the Microculture Tetrazolium Test (MTT) proliferation assay were performed to appraise the effects of celecoxib and TMZ. Results: demonstrated the upregulation of NF-κB p65 (RelA) and TNFα and celecoxib reduced the viability of the human glioblastoma cell line SF-767, cell proliferation, and NF-κB p65 (RelA) and TNFα expression in a dose-dependent manner. Overall, these findings demonstrate for the first time how celecoxib therapy could mitigate the invasive characteristics of the human GBM cell line SF-767 by inhibiting the NF-κB mediated stimulation of the inflammatory cascade. Conclusion: based on current findings, we propose that celecoxib as a drug candidate in combination with temozolomide might dampen the transcriptional and enzymatic activities associated with the aggressiveness of GBM and reduce the expression of GBM-associated NF-κB p65 (RelA) and TNFα inflammatory genes expression.
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spelling pubmed-106077962023-10-28 Celecoxib Suppresses NF-κB p65 (RelA) and TNFα Expression Signaling in Glioblastoma Ahsan, Hina Malik, Shaukat Iqbal Shah, Fawad Ali El-Serehy, Hamed A. Ullah, Amin Shah, Zafar Abbas J Clin Med Article Background: Glioblastoma (GBM) harbors significant genetic heterogeneity, high infiltrative capacity, and patterns of relapse following many therapies. The expression of nuclear factor kappa-B (NF-κB p65 (RelA)) and signaling pathways is constitutively activated in GBM through inflammatory stimulation such as tumor necrosis factor-alpha (TNFα), cell invasion, motility, abnormal physiological stimuli, and inducible chemoresistance. However, the underlying anti-tumor and anti-proliferative mechanisms of NF-κB p65 (RelA) and TNFα are still poorly defined. This study aimed to investigate the expression profiling of NF-κB p65 (RelA) and TNFα as well as the effectiveness of celecoxib along with temozolomide (TMZ) in reducing the growth of the human GBM cell line SF-767. Methods: genome-wide expression profiling, enrichment analysis, immune infiltration, quantitative expression, and the Microculture Tetrazolium Test (MTT) proliferation assay were performed to appraise the effects of celecoxib and TMZ. Results: demonstrated the upregulation of NF-κB p65 (RelA) and TNFα and celecoxib reduced the viability of the human glioblastoma cell line SF-767, cell proliferation, and NF-κB p65 (RelA) and TNFα expression in a dose-dependent manner. Overall, these findings demonstrate for the first time how celecoxib therapy could mitigate the invasive characteristics of the human GBM cell line SF-767 by inhibiting the NF-κB mediated stimulation of the inflammatory cascade. Conclusion: based on current findings, we propose that celecoxib as a drug candidate in combination with temozolomide might dampen the transcriptional and enzymatic activities associated with the aggressiveness of GBM and reduce the expression of GBM-associated NF-κB p65 (RelA) and TNFα inflammatory genes expression. MDPI 2023-10-23 /pmc/articles/PMC10607796/ /pubmed/37892820 http://dx.doi.org/10.3390/jcm12206683 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ahsan, Hina
Malik, Shaukat Iqbal
Shah, Fawad Ali
El-Serehy, Hamed A.
Ullah, Amin
Shah, Zafar Abbas
Celecoxib Suppresses NF-κB p65 (RelA) and TNFα Expression Signaling in Glioblastoma
title Celecoxib Suppresses NF-κB p65 (RelA) and TNFα Expression Signaling in Glioblastoma
title_full Celecoxib Suppresses NF-κB p65 (RelA) and TNFα Expression Signaling in Glioblastoma
title_fullStr Celecoxib Suppresses NF-κB p65 (RelA) and TNFα Expression Signaling in Glioblastoma
title_full_unstemmed Celecoxib Suppresses NF-κB p65 (RelA) and TNFα Expression Signaling in Glioblastoma
title_short Celecoxib Suppresses NF-κB p65 (RelA) and TNFα Expression Signaling in Glioblastoma
title_sort celecoxib suppresses nf-κb p65 (rela) and tnfα expression signaling in glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10607796/
https://www.ncbi.nlm.nih.gov/pubmed/37892820
http://dx.doi.org/10.3390/jcm12206683
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