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We recently demonstrated in vitro that curcumin can prevent oncogenic profile of bile in human hypopharyngeal cells, by inhibiting NF\u2010\u03baB. We hypothesize that topically applied curcumin to the hypopharynx can similarly block early oncogenic molecular events of bile, by inhibiting NF\u2010<jats:italic>\u03ba<\/jats:italic>B and consequently altering the expression of genes with oncogenic function. Using <jats:italic>Mus musculus<\/jats:italic> (C57Bl\/6J), we topically applied curcumin (250\u00a0\u03bcmol\/L; three times per day; 10\u00a0days) to the hypopharynx, 15\u00a0minutes before, 15\u00a0minutes after or in combination with bile acids (pH 3.0). Immunohistochemical analysis and qPCR revealed that topically applied curcumin either before, after or in combination with acidic bile exposure significantly suppressed its induced NF\u2010\u03baB activation in regenerating epithelial cells, and overexpression of <jats:italic>Rela, Bcl2, Egfr, Stat3, Wnt5a, Tnf, Il6, Ptgs2. Akt1<\/jats:italic> was particularly inhibited by curcumin when applied simultaneously with bile. We provide novel evidence into the preventive and therapeutic properties of topically applied curcumin in acidic bile\u2010induced early oncogenic molecular events in hypopharyngeal mucosa, by inhibiting NF\u2010\u03baB, and shaping future translational development of effective targeted therapies using topical non\u2010pharmacologic inhibitors of NF\u2010\u03baB.<\/jats:p>","DOI":"10.1111\/jcmm.15640","type":"journal-article","created":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T09:43:06Z","timestamp":1595324586000},"page":"10311-10321","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The in vivo preventive and therapeutic properties of curcumin in bile reflux\u2010related oncogenesis of the hypopharynx"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1840-659X","authenticated-orcid":false,"given":"Sotirios 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