In vitro model for gastroduodenal reflux–induced nuclear factor‐kappaB activation and its role in hypopharyngeal carcinogenesis. (11th November 2015)

• Record Type: Journal Article
• Authors: Sasaki, Clarence T.; Issaeva, Natalia; Vageli, Dimitra P.
• Is Part Of: Head & neck. Volume 38(2016)Supplement 1
• Page Start: E1381
• Page End: E1391
• Publication Date: 2015-11-11
• Subjects: gastroduodenal reflux -- bile acids -- nuclear factor‐kappa B (NF‐κB) -- hypopharyngeal cancer -- in vitro; Head -- Diseases -- Periodicals; Neck -- Diseases -- Periodicals; Head -- Periodicals; Neck -- Periodicals; Face -- Periodicals; 617.51059
• DOI: 10.1002/hed.24231
• Languages: English
• ISSNs: 1043-3074

Abstract

Abstract: 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