INVESTIGATION OF THE MECHANISM AND THERAPEUTIC POTENTIAL OF A TRANSCRIPTION FACTOR DECOY TARGETING SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION-3 (STAT3) FOR SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK (SCCHN)
作者： Amanda L. Boehm
DOI:
关键词: Cancer research 、 STAT1 、 EGFR inhibitors 、 STAT3 、 STAT protein 、 Decoy 、 Biology 、 Transcription factor 、 DNA-binding domain 、 Growth inhibition
摘要: Squamous cell carcinoma of the head and neck (SCCHN) is 5th most common cancer worldwide. Signal transducer activator transcription 3 (STAT3) overexpressed in SCCHN associated with decreased survival. A factor decoy was designed to bind DNA binding domain STAT3, abrogating expression downstream target genes. The antitumor mechanisms decoys, including STAT3 decoy, are incompletely understood. forms heterodimers STAT1 suggesting that may interact STAT1. We determined pathway functional lines. inhibited STAT1-mediated gene, IRF-1. Stimulation IFN-ƒ× did not mitigate decoy-mediated growth inhibition. inhibition signaling abrogate its effects vitro. Studies using knockout cells indicated necessary for then studied combination an EGFR inhibitor and/or a Bcl-XL as therapeutic strategy SCCHN. Targeting this at several levelsiXthe upstream receptor (EGFR), intracellular (STAT3), gene (Bcl-XL)iXhas been previously investigated. Combined targeting erlotinib enhanced gossypol, inhibitor, resulted triple all agents These results indicate EGFR-STAT3-Bcl-XL three distinct levels be promising treatment
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