J Cancer 2020; 11(10):3013-3019. doi:10.7150/jca.40744

Research Paper

A thioredoxin reductase inhibitor ethaselen induces growth inhibition and apoptosis in gastric cancer

Wang Wu1,2, Zhiying Yang1, Xing Xiao1, Tailai An1,2, Bo Li1, Jun Ouyang1,2, Huafu Li1,2, Chunming Wang1,2, Yawei Zhang1,2, Haiyong Zhang1,2, Yulong He1,2✉, Changhua Zhang1,2✉

1. Center for Digestive Disease, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, 518107, China
2. Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China

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Wu W, Yang Z, Xiao X, An T, Li B, Ouyang J, Li H, Wang C, Zhang Y, Zhang H, He Y, Zhang C. A thioredoxin reductase inhibitor ethaselen induces growth inhibition and apoptosis in gastric cancer. J Cancer 2020; 11(10):3013-3019. doi:10.7150/jca.40744. Available from http://www.jcancer.org/v11p3013.htm

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Gastric cancer (GC) is the third leading cause of cancer deaths worldwide. Conventional chemotherapy has been proven useful to only a portion of the patients. Previous developed targeted drugs are more effective and tolerable than conventional drugs. Thus the development of novel drugs targeting markers is an urgent task and the main direction for future research. Ethaselen, an inhibitor of thioredoxin reductase (TrxR), has been considered an important anticancer target drug. Previous studies show that it is effective on treating many kinds of cancers. In this paper, we examined that ethaselen effectively inhibited the growth of gastric cancer cells and promoted apoptosis. Organoids were cultured from patient-derived cells in a three-dimension form which are widely used in cancer research to help us understand cancer cells behavior at the sub-organ level and develop novel drugs. We established a drug testing and screening system using GC-derived organoids by recapitulating tumor microenvironment. We confirmed that the TrxR-targeting ethaselen could be a novel and effective drug for gastric cancer treatment.