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J Cancer 2017; 8(18):3876-3886. doi:10.7150/jca.20380 This issue Cite

Research Paper

Aqueous Huaier Extract Suppresses Gastric Cancer Metastasis and Epithelial to Mesenchymal Transition by Targeting Twist

Zhiyuan Xu^1*, Guowei Zheng^1*, Yiping Wang², Chunli Zhang³, Jianfa Yu¹, Fei Teng¹, Hang Lv^2✉, Xiangdong Cheng^1✉

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

✉ Corresponding authors: Name: Xiangdong Cheng, Department of gastrointestinal Surgery, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Youdian Road 54#, Hangzhou, 310006, Zhejiang, China. Tel: +86-571-87070965; Fax: +86-571-87070965; E-mail: getfaredu.cn Name: Hang Lv, Key Laboratory of integrated traditional Chinese and Western Medicine for diagnosis and treatment of digestive system tumor, Youdian Road 54#, Hangzhou, 310006, Zhejiang, China. Tel: +86-571-87070965; Fax: +86-571-87070965; E-mail: lhcid21com More

Abstract

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.

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