The temporal effects of topical NF-?B inhibition, in the in vivo prevention of bile-related oncogenic mRNA and miRNA phenotypes in murine hypopharyngeal mucosa: a preclinical model.

ABSTRACT: Supraesophageal bile reflux at strongly acidic pH can cause hypopharyngeal squamous cell cancer, through activation of the oncogenic NF-?B-related pathway. We hypothesize that topical pre- or post-application of pharmacologic NF-?B inhibitor, BAY 11-7082 (0.25 ?mol), on murine (C57BL/6J) HM (twice a day for 10 days) can effectively inhibit acidic bile (10 mmol/l; pH 3.0) induced oncogenic molecular events, similar to prior in vitro findings. We demonstrate that the administration of BAY 11-7082, either before or after acidic bile, eliminates NF-?B activation, prevents overexpression of Bcl2, Rela, Stat3, Egfr, Tnf, Wnt5a, and deregulations of miR-192, miR-504, linked to bile reflux-related hypopharyngeal cancer. Pre- but not post-application of NF-?B inhibitor, significantly blocks overexpression of Il6 and prostaglandin H synthases 2 (Ptgs2), and reverses miR-21, miR-155, miR-99a phenotypes, supporting its early bile-induced pro-inflammatory effect. We thus provide novel evidence that topical administration of a pharmacological NF-?B inhibitor, either before or after acidic bile exposure can successfully prevent its oncogenic mRNA and miRNA phenotypes in HM, supporting the observation that co-administration of NF-?B inhibitor may not be essential in preventing early bile-related oncogenic events and encouraging a capacity for further translational exploration.

SUBMITTER: Vageli DP 

PROVIDER: S-EPMC7476734 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature