Cirsiliol targets tyrosine kinase 2 to inhibit esophageal squamous cell carcinoma growth in vitro and in vivo

BackgroundEsophageal squamous cell carcinoma (ESCC) is an aggressive and lethal cancer with a low 5 year survival rate. Identification of new therapeutic targets and its inhibitors remain essential for ESCC prevention and treatment.MethodsTYK2 protein levels were checked by immunohistochemistry. The function of TYK2 in cell proliferation was investigated by MTT [(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and anchorage-independent cell growth. Computer docking, pull-down assay, surface plasmon resonance, and kinase assay were used to confirm the binding and inhibition of TYK2 by cirsiliol. Cell proliferation, western blot and patient-derived xenograft tumor model were used to determine the inhibitory effects and mechanism of cirsiliol in ESCC.ResultsTYK2 was overexpressed and served as an oncogene in ESCC. Cirsiliol could bind with TYK2 and inhibit its activity, thereby decreasing dimer formation and nucleus localization of signal transducer and activator of transcription 3 (STAT3). Cirsiliol could inhibit ESCC growth in vitro and in vivo.ConclusionsTYK2 is a potential target in ESCC, and cirsiliol could inhibit ESCC by suppression of TYK2.

Automated summary

The study found that TYK2 is overexpressed and acts as an oncogene in esophageal squamous cell carcinoma; Cirsiliol can bind to TYK2 and inhibit its activity, reducing dimer formation and nucleus localization of STAT3; Cirsiliol can inhibit the growth of esophageal squamous cell carcinoma in vitro and in vivo.