Background: Esophageal 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. Methods: TYK2 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. Results: TYK2 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. Conclusions: TYK2 is a potential target in ESCC, and cirsiliol could inhibit ESCC by suppression of TYK2.
|Original language||English (US)|
|Journal||Journal of Experimental and Clinical Cancer Research|
|State||Published - Dec 2021|
Bibliographical noteFunding Information:
This work was supported by the national science foundation of China (No. 81572812; No. 81872335); Henan Key Science and Technology Program 161100510300; National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program”, China (No. 2018ZX09711002).
© 2021, The Author(s).
- Esophageal squamous cell carcinoma
- Patient-derived xenograft
- Surface plasmon resonance