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In vitro model for gastroduodenal reflux–induced nuclear factor‐kappaB activation and its role in hypopharyngeal carcinogenesis
Author(s) -
Sasaki Clarence T.,
Issaeva Natalia,
Vageli Dimitra P.
Publication year - 2016
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.24231
Subject(s) - carcinogenesis , cancer research , biology , oncogene , head and neck squamous cell carcinoma , stat protein , stat3 , cell , signal transduction , cancer , cell cycle , head and neck cancer , microbiology and biotechnology , genetics
Background The purpose of this study was to investigate whether gastroduodenal reflux can play a role in the pathogenesis of hypopharyngeal cancer; therefore, we assessed its effect on the nuclear factor‐kappa B (NF‐κB) pathway, as similarly noted in the esophagus. Methods We exposed human cells derived from the hypopharyngeal epithelium to bile acids or deoxycholic acid. We centered our study on the transcriptional activation of NF‐κB pathway, previously linked to head and neck squamous cell carcinoma (HNSCC). Results We show that acidic‐bile salts induce: (1) NF‐κB activation with high cytoplasmic Bcl‐2 expression; (2) significant increase in expression v‐rel avian reticuloendotheliosis viral oncogene homolog A (RELA(p65)), v‐rel avian reticuloendotheliosis viral oncogene homolog (c‐REL) signal transducer and activator of transcription 3 (STAT3), isoform of transformation related protein p63 (ΔNp63), B‐cell lymphoma 2 (Bcl‐2), tumor necrosis factor alpha (TNF‐α), epidermal growth factor receptor (EGFR), and wingless type MMTV integration site family member 5A (WNT5A) and a decrease in tumor protein p53 (Tp53); and (3) phenotypic changes that are similar to the phenotype of the untreated hypopharyngeal cancer cell line, University of Michigan squamous cell carcinoma (UMSCC)‐11B. These changes are not seen when cells were exposed to neutral control or acid alone. Conclusion Our findings in vitro are consistent with the hypothesis that gastroduodenal reflux plays a role in hypopharyngeal carcinogenesis and its effect is mediated through activation of NF‐κB pathway. © 2015 Wiley Periodicals, Inc. Head Neck 38 : E1381–E1391, 2016