Jiang Ying, Wang Wei, Wu Xi, Shi Jihua
Department of Gastroenterology, National Center of Gerontology, Beijing Hospital, Beijing 100730, P.R. China.
Exp Ther Med. 2020 Feb;19(2):817-824. doi: 10.3892/etm.2019.8308. Epub 2019 Dec 9.
Gastric cancer is the fifth most common malignancy and the third highest cause of cancer-associated mortality worldwide. Therefore, research on the pathogenesis of gastric cancer is of utmost importance. It has been reported that aberrant activation of the Wnt/β-catenin signaling pathway is involved in the occurrence and development of gastric cancer. In the present study, it was found that pizotifen could inhibit the viability of gastric cancer cell lines MNK45 and AGS cells in a dose-dependent manner. Pizotifen treatment suppressed cell migration and invasion in MNK45 and AGS cells, whilst also inducing apoptosis. Western blot analysis demonstrated that pizotifen blocked the expression of Wnt3a, β-catenin and N-cadherin, whilst increasing E-cadherin expression. In addition, BML-284, a pharmacological Wnt signaling activator, partially reversed the changes in the expression levels of β-catenin, N-cadherin and E-cadherin in MNK45 and AGS cells induced by pizotifen. Collectively, these findings suggested that pizotifen demonstrates potential as a novel anti-cancer drug for the treatment of gastric cancer by inhibiting the Wnt/β-catenin pathway.
胃癌是全球第五大常见恶性肿瘤，也是癌症相关死亡的第三大原因。因此，对胃癌发病机制的研究至关重要。据报道，Wnt/β-连环蛋白信号通路的异常激活与胃癌的发生和发展有关。在本研究中，发现苯噻啶能以剂量依赖的方式抑制胃癌细胞系MNK45和AGS细胞的活力。苯噻啶处理可抑制MNK45和AGS细胞的迁移和侵袭，同时诱导细胞凋亡。蛋白质免疫印迹分析表明，苯噻啶可阻断Wnt3a、β-连环蛋白和N-钙黏蛋白的表达，同时增加E-钙黏蛋白的表达。此外，药理学Wnt信号激活剂BML-284部分逆转了苯噻啶诱导的MNK45和AGS细胞中β-连环蛋白、N-钙黏蛋白和E-钙黏蛋白表达水平的变化。总的来说，这些发现表明苯噻啶通过抑制Wnt/β-连环蛋白途径，具有作为一种新型抗癌药物治疗胃癌的潜力。
