Thymoquinone induces cytotoxicity and reprogramming of EMT in gastric cancer cells by targeting PI3K/Akt/mTOR pathway
Thymoquinone induces cytotoxicity and reprogramming of EMT in gastric cancer cells by targeting PI3K/Akt/mTOR pathway
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DOI：
10.1007/s12038-017-9708-3
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发表时间：
2017-12-01
影响因子：
2.9
通讯作者：
Huang, Qing-Xian
中科院分区：
文献类型：
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作者：
Feng, Li-Min;Wang, Xue-Feng;Huang, Qing-Xian
胃癌是世界范围内癌症相关死亡的致命原因之一。该病在我国的发病率和死亡率较高。本研究观察了百里醌（Thymoquinone，TQ）对胃癌细胞（MGC-80 -3和SGC-7901）和正常非癌细胞GES-1的抗肿瘤作用，并探讨了其作用机制。结果表明，TQ对胃癌细胞株MGC-80 -3和SGC-7901具有明显的生长抑制作用。然而，对正常GES-1细胞观察到较低的细胞毒性。TQ能抑制MGC 80 -3和SGC-7901细胞的殖民地形成能力，并呈剂量依赖性。TQ还抑制胃癌细胞的细胞迁移能力，下调间充质基因如N-cadherin、Vimentin和TWIST的表达。然而，上皮标志物，如E-钙粘蛋白和细胞角蛋白-19（CK 19）明显上调，在TQ处理的胃癌细胞。由于PI 3 K/Akt/mTOR信号通路在胃癌的发生、发展过程中起重要作用，因此我们也研究了TQ对胃癌细胞PI 3 K/Akt/mTOR信号通路的影响。观察到TQ下调该途径的一些关键蛋白的表达。因此，TQ有可能成为治疗胃癌的先导分子。
Gastric cancer is one of the lethal causes of cancer-related deaths worldwide. The incidence and mortality rates of this disease is comparatively higher in China. In the current study, we evaluated the anticancer effects of Thymoquinone (TQ) against gastric cancer cells (MGC80-3 and SGC-7901) and normal noncancerous GES-1 cells and attempted to investigate the underlying mechanism. Our results indicated that TQ exhibited significant growth inhibitory effects on gastric cancer cells (MGC80-3 and SGC-7901). However, lower cytotoxicity was observed against normal GES-1 cells. Moreover, TQ could inhibit the colony formation potential of MGC80-3 and SGC-7901 cells in a dose-dependent manner. TQ also inhibited cell migration ability of the gastric cancer cells and down-regulated the expression of the mesenchymal genes such as N-cadherin, Vimentin, and TWIST. However, the epithelial markers such as E-cadherin and cytokeratin-19 were distinctly up-regulated in TQ-treated gastric cancer cells. Since PI3K/Akt/mTOR plays an important role in progression and tumorigenesis, we also investigated the effect of TQ on PI3K/Akt/mTOR signalling pathway in gastric cancer cells. It was observed that TQ down-regulated the expression of some of the key proteins of this pathway. Taken together, we conclude that TQ may prove lead molecule for the treatment of gastric cancer.