J Cancer 2017; 8(18):3876-3886. doi:10.7150/jca.20380
Aqueous Huaier Extract Suppresses Gastric Cancer Metastasis and Epithelial to Mesenchymal Transition by Targeting Twist
1. Department of gastrointestinal surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China;
2. Key Laboratory of integrated traditional Chinese and Western Medicine for diagnosis and treatment of digestive system tumor, Hangzhou, Zhejiang, China;
3. Department of pathology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
* Zhiyuan Xu and Guowei Zheng contributed equally to this work
Xu Z, Zheng G, Wang Y, Zhang C, Yu J, Teng F, Lv H, Cheng X. Aqueous Huaier Extract Suppresses Gastric Cancer Metastasis and Epithelial to Mesenchymal Transition by Targeting Twist. J Cancer 2017; 8(18):3876-3886. doi:10.7150/jca.20380. Available from http://www.jcancer.org/v08p3876.htm
Trametes robiniophila Murr. (Huaier) is a widely used anti-cancer agent in China. Strong evidence for the anti-proliferative activity of Huaier has been reported; however, its anti-metastatic potential against gastric cancer (GC) as well as its underlying mechanism of action are unknown. Here, we show that treatment with an aqueous Huaier extract over a range of concentrations significantly suppressed both the invasiveness and migratory ability of GC cells. Huaier could also partly reverse the epithelial-mesenchymal transition (EMT), as characterized by increased expression of the epithelial marker E-cadherin and decreased expression of the mesenchymal markers N-cadherin and vimentin. In addition, Huaier-treated cells expressed lower levels of Twist compared to untreated controls, and overexpression of Twist via transfection could partially abolish the anti-metastatic activity of Huaier. Furthermore, elevated Twist expression was correlated with an advanced TNM stage, a high rate of lymph node metastasis, and reduced disease-free survival in GC patients. These findings reveal a novel anti-metastatic mechanism for Huaier, which inhibits the EMT by targeting Twist, suggesting its potential application against a GC relapse.
Keywords: gastric cancer, Huaier, metastasis, epithelial-mesenchymal transition.