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Targeting STAT3 prevents bile reflux-induced oncogenic molecular events linked to hypopharyngeal carcinogenesis
Acidic bile induces aberrant activation of signal transducer and activator of transcription 3 (STAT3) oncogene in hypopharyngeal cells. Targeting the STAT3 pathway, by knocking down STAT3 (STAT3 siRNA) or its pharmacologic inhibition by blocking STAT3 phosphorylation (Nifuroxazide) or dimerization (SI3‐201; STA‐21), significantly suppressed acidic bile‐induced STAT3 activation and its transcriptional activity, Bcl‐2 overexpression, transcriptional activation of IL6, TNF‐α, BCL2, EGFR, STAT3, RELA(p65), REL and WNT5A, and cell survival. Our novel findings document the important role of STAT3 in bile reflux‐related molecular oncogenic events, which can be dramatically prevented by STAT3 silencing. STA‐21, SI3‐201, or Nifuroxazide effectively inhibited STAT3 and cancer‐related inflammatory phenotype, encouraging their single or combined application in preventive or therapeutic strategies of bile reflux‐related hypopharyngeal carcinogenesis.
Source: Wiley