RESUMO
Bile at strongly acidic pH exerts a carcinogenic effect on the hypopharynx, based upon recent pre-clinical studies that support its role as an independent risk factor. We recently demonstrated in vitro that curcumin can prevent oncogenic profile of bile in human hypopharyngeal cells, by inhibiting NF-κB. We hypothesize that topically applied curcumin to the hypopharynx can similarly block early oncogenic molecular events of bile, by inhibiting NF-κB and consequently altering the expression of genes with oncogenic function. Using Mus musculus (C57Bl/6J), we topically applied curcumin (250 µmol/L; three times per day; 10 days) to the hypopharynx, 15 minutes before, 15 minutes 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-κB activation in regenerating epithelial cells, and overexpression of Rela, Bcl2, Egfr, Stat3, Wnt5a, Tnf, Il6, Ptgs2. Akt1 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-induced early oncogenic molecular events in hypopharyngeal mucosa, by inhibiting NF-κB, and shaping future translational development of effective targeted therapies using topical non-pharmacologic inhibitors of NF-κB.
Assuntos
Refluxo Biliar/tratamento farmacológico , Refluxo Biliar/prevenção & controle , Carcinogênese/patologia , Curcumina/uso terapêutico , Hipofaringe/patologia , Animais , Bile/metabolismo , Refluxo Biliar/patologia , Carcinogênese/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Curcumina/administração & dosagem , Curcumina/farmacologia , Feminino , Antígeno Ki-67/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Mucosa/efeitos dos fármacos , Mucosa/patologia , NF-kappa B/metabolismo , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
OBJECTIVE: To investigate the therapeutical effect of Canghuopingwei Granules on chronic gastritis in rats. METHODS: Rat models of chronic gastritis and bile reflux gastritis were used. After rat models were established, the rats were divided into 6 groups and were treated with different drugs. The tissue samples were obtained after one week. The volume of gastric juice, acidity of gastric juice and pepsase activity were determined, and changes of the gastric mucosa were studied by microscopy. RESULTS: The acidity of gastric juice was reversed with Canghuopingwei granules treatment. Gastric pathologic examination suggested that Canghuopingwei granules could markedly attenuate the pathological changes of gastric mucosa in rats. CONCLUSION: Canghuopingwei granules has remarkably therapeutical effect on chronic gastritis and bile reflux gastritis in rats.