Oncotarget: The temporal effects of topical NF-κB inhibition: a preclinical model

 The cover for issue 35 of Oncotarget features Figure 4, "The in vivo pre- or post- topical application of BAY 11-7082 prevents the acidic bile-induced deregulation of cancer-related miRNA markers in 10-day exposed murine HM," by Vageli, et al. reported that Supraesophageal bile reflux at strongly acidic pH can cause hypopharyngeal squamous cell cancer, through activation of the oncogenic NF-κB-related pathway.


The authors hypothesize that topical pre- or post-application of pharmacologic NF-κB inhibitor, BAY 11-7082, on murine HM can effectively inhibit acidic bile induced oncogenic molecular events, similar to prior in vitro findings.


They demonstrate that the administration of BAY 11-7082, either before or after acidic bile, eliminates NF-κB 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-κB inhibitor, significantly blocks overexpression of Il6 and prostaglandin H synthases 2, and reverses miR-21, miR-155, miR-99a phenotypes, supporting its early bile-induced pro-inflammatory effect.


The authors thus provide novel evidence that topical administration of a pharmacological NF-κB 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-κB inhibitor may not be essential in preventing early bile-related oncogenic events and encouraging a capacity for further translational exploration.

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