Wu Wang, Yang Zhiying, Xiao Xing, An Tailai, Li Bo, Ouyang Jun, Li Huafu, Wang Chunming, Zhang Yawei, Zhang Haiyong, He Yulong, Zhang Changhua
Center for Digestive Disease, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, 518107, China.
Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
J Cancer. 2020 Mar 4;11(10):3013-3019. doi: 10.7150/jca.40744. eCollection 2020.
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.
胃癌(GC)是全球癌症死亡的第三大主要原因。传统化疗仅对部分患者有效。先前开发的靶向药物比传统药物更有效且耐受性更好。因此,开发针对标志物的新型药物是一项紧迫任务,也是未来研究的主要方向。乙磺硒,一种硫氧还蛋白还原酶(TrxR)抑制剂,被认为是一种重要的抗癌靶向药物。先前的研究表明它对多种癌症的治疗有效。在本文中,我们研究发现乙磺硒能有效抑制胃癌细胞的生长并促进其凋亡。类器官是从患者来源的细胞以三维形式培养而成,在癌症研究中广泛应用,以帮助我们了解亚器官水平的癌细胞行为并开发新型药物。我们通过重现肿瘤微环境,建立了一个使用源自胃癌的类器官的药物测试和筛选系统。我们证实,靶向TrxR的乙磺硒可能是一种用于胃癌治疗的新型有效药物。