Temporal characteristics of NF-κB inhibition in blocking bile-induced oncogenic molecular events in hypopharyngeal cells


The cover for issue 36 of Oncotarget features Figure 6, "Schematic representation of pre- and post-application of NF-κB inhibitor (BAY 11-7082) in acidic bile-exposed MHPC," by Doukas, et al.

The scientists previously showed the key role NF- B in mediating acidic bile-induced pre-neoplastic events in hypopharyngeal cells, and that co-administration of specific NF- B inhibitor, BAY 11-7082, together with acidic bile, can effectively prevent its related oncogenic molecular effects.

Their observations support the understanding that acidic bile-induced deregulation of anti-apoptotic or oncogenic factors, bcl-2, STAT3, EGFR, IL-6, WNT5A, mi R-21, mi R-155, mi R-375, is highly NF- B-dependent, showing that even post-application of inhibitor can suppress their deregulation.

Dr. Clarence T. Sasaki from the The Yale Larynx Laboratory, Department of Surgery at the Yale School of Medicine in New Haven, CT, USA said, "Laryngopharyngeal reflux (LPR) has been linked to chronic inflammatory and neoplastic diseases of the upper aero-digestive tract."

Figure 1: Pre- or post-application of BAY 11-7082 inhibits the acidic bile-induced nuclear translocation of phospho-NF-?B in MHPC.

In this connection, the authors have previously shown that acidic bile is capable of upregulating NF- B signaling and transcriptionally activating oncogenic factors while deregulating cancer-related mi RNA markers in exposed hypopharyngeal primary cells.

They hypothesize that treatment of hypopharyngeal cells with BAY 11-7082 before or after acidic bile exposure may have effects comparable to its co-administration with acidic bile in inhibiting its oncogenic mRNA and mi RNA phenotypes.

The Sasaki Research Team concluded, "our novel findings show that short duration application of pharmacologic inhibitor of NF-κB 15 min before or after acidic bile exposure comparably prevents and suppresses its mRNA and miRNA oncogenic phenotypes in treated murine hypopharyngeal primary cells. In practical terms these observations strongly support the future clinical use of a topical NF-κB inhibitor in suppressing bile-induced oncogenic molecular events. Our data further provide a novel window of observation into the complex kinetics of an interesting mechanistic link between acidic bile and early neoplasia."

Full text - https://www.oncotarget.com/article/26917/text/

Correspondence to - Clarence T. Sasaki - [email protected]

Keywords - NF-κB inhibition, STAT3, miR-21, bile reflux, hypopharyngeal cancer

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