Inhibition of NF-κ B prevents the acidic bile-induced oncogenic mRNA phenotype, in human hypopharyngeal cells

Oncotarget
Dimitra P VageliClarence T Sasaki

Abstract

Bile-containing gastro-duodenal reflux has been clinically considered an independent risk factor in hypopharyngeal carcinogenesis. We recently showed that the chronic effect of acidic bile, at pH 4.0, selectively induces NF-κB activation and accelerates the transcriptional levels of genes, linked to head and neck cancer, in normal hypopharyngeal epithelial cells. Here, we hypothesize that NF-κB inhibition is capable of preventing the acidic bile-induced and cancer-related mRNA phenotype, in treated normal human hypopharyngeal cells. In this setting we used BAY 11-7082, a specific and well documented pharmacologic inhibitor of NF-κB, and we observed that BAY 11-7082 effectively inhibits the acidic bile-induced gene expression profiling of the NF-κB signaling pathway (down-regulation of 72 out of 84 analyzed genes). NF-κB inhibition significantly prevents the acidic bile-induced transcriptional activation of NF-κB transcriptional factors, RELA (p65) and c-REL, as well as genes related to and commonly found in established HNSCC cell lines. These include anti-apoptotic bcl-2, oncogenic STAT3, EGFR, ∆Np63, TNF-α and WNT5A, as well as cytokines IL-1β and IL-6. Our findings are consistent with our hypothesis demonstrating that NF-κB i...Continue Reading

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Citations

Jul 22, 2020·Journal of Cellular and Molecular Medicine·Sotirios G DoukasDimitra Vageli
Sep 27, 2018·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Weiheng WenJia Sun
Jun 8, 2019·Cancer Medicine·Sotirios G DoukasClarence T Sasaki
Sep 25, 2021·Oncology Reports·Dimitra P VageliBenjamin L Judson
Dec 2, 2021·Journal of Cellular and Molecular Medicine·Dimitra P VageliBenjamin L Judson
Dec 4, 2021·European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery·Yading LiJianning Zhang

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Methods Mentioned

BETA
nuclear translocation
PCR
Protein Assay
Assay
transfection

Software Mentioned

RT 2 - Profiler PCR Array Data Analysis
[UNK]
Zen imaging
Zen
Image Lab
GraphPad
GraphPad Prism
Graph Pad Prism

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