High-Content pSTAT3/1 Imaging Assays to Screen for Selective Inhibitors of STAT3 Pathway Activation in Head and Neck Cancer Cell Lines

摘要: ABSTRACT The oncogenic transcription factor signal transducer and activator of 3 (STAT3) is hyperactivated in most cancers represents a plausible therapeutic target. In the absence STAT3-selective small-molecule inhibitors, we sought to develop pSTAT3/1 high-content imaging (HCS) assays screen for selective inhibitors STAT3 pathway activation head neck squamous cell carcinomas (HNSCC) tumor lines. Based on expression interleukin-6 (IL-6)Rα gp130 subunits IL-6 receptor complex STAT3, selected Cal33 HNSCC line as our model. After developing image acquisition analysis procedures, rigorously investigated cytokine responses optimize dynamic ranges both demonstrated that pan-Janus kinase inhibitor pyridone 6 nonselectively inhibited pSTAT3 pSTAT1 with 50% inhibition concentrations 7.19±4.08 16.38±8.45 nM, respectively. optimized HCS assay performed very wel...