Jia Xuechao, Huang Chuntian, Hu Yamei, Wu Qiong, Liu Fangfang, Nie Wenna, Chen Hanyong, Li Xiang, Dong Zigang, Liu Kangdong
Department of Pathophysiology, The School of Basic Medical Sciences, AMS, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China.
China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China.
J Exp Clin Cancer Res. 2021 Mar 17;40(1):105. doi: 10.1186/s13046-021-01903-z.
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.
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.
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.
TYK2 is a potential target in ESCC, and cirsiliol could inhibit ESCC by suppression of TYK2.
食管鳞状细胞癌（ESCC）是一种侵袭性强且致命的癌症，5年生存率低。鉴定新的治疗靶点及其抑制剂对于ESCC的预防和治疗仍然至关重要。
通过免疫组织化学检测TYK2蛋白水平。采用MTT [（4,5 - 二甲基噻唑 - 2 - 基）- 2,5 - 二苯基四氮唑溴盐]和非锚定依赖性细胞生长研究TYK2在细胞增殖中的作用。利用计算机对接、下拉实验、表面等离子体共振和激酶实验来证实cirsiliol对TYK2的结合和抑制作用。采用细胞增殖、蛋白质印迹法和患者来源的异种移植肿瘤模型来确定cirsiliol对ESCC的抑制作用及其机制。
TYK2在ESCC中过表达并作为癌基因发挥作用。Cirsiliol可与TYK2结合并抑制其活性，从而减少信号转导和转录激活因子3（STAT3）的二聚体形成和核定位。Cirsiliol可在体外和体内抑制ESCC生长。
TYK2是ESCC的一个潜在靶点，cirsiliol可通过抑制TYK2来抑制ESCC。
