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首页> 外文期刊>Integrative cancer therapies. >Antimetastatic Effects of Celastrus orbiculatus on Human Gastric Adenocarcinoma by Inhibiting Epithelial–Mesenchymal Transition and NF-κB/Snail Signaling Pathway
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Antimetastatic Effects of Celastrus orbiculatus on Human Gastric Adenocarcinoma by Inhibiting Epithelial–Mesenchymal Transition and NF-κB/Snail Signaling Pathway

机译：通过抑制上皮-间充质转化和NF-κB/ Snail信号通路对人胃腺癌的抑癌作用

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Aim of the Study. Celastrus orbiculatus has been used as a folk medicine in China for the treatment of many diseases. In the laboratory, the ethyl acetate extract of Celastrus orbiculatus (COE) displays a wide range of anticancer functions. However, the inhibition of the metastasis mechanism of COE in gastric cancer cells has not been investigated so far. The present study was undertaken to determine if the antimetastatic effects of COE were involved in inhibition of the epithelial–mesenchymal transition (EMT) of human gastric adenocarcinoma SGC-7901 cells. Methods. The adhesion, invasion, and migration of SGC-7901 cells were determined by COE treatment in vitro, using Matrigel-coated plate, transwell membrane chamber, and wound healing models, respectively. In vivo, the growth-inhibiting and antimetastatic effects of COE on the nude mice model of gastric cancer were tested and the mechanisms were explored. The expression of EMT markers and nuclear factor κB (NF-κB)/Snail signaling pathway were evaluated by using western blotting and immunohistochemistry. Results. Treatment with COE dose-dependently inhibited the proliferation, adhesion, invasion, and migration of SGC-7901 cells in vitro, which was realized by enhancing the expression of E-cadherin and reducing N-cadherin and vimentin expression. Moreover, COE suppressed the activation of NF-κB/Snail signaling pathway induced by tumor necrosis factor-α. In addition, COE effectively suppressed tumor growth and metastasis in the nude mice model due to reduced expression of N-cadherin, vimentin, NF-κB p65, and Snail and increased expression of E-cadherin in the tumor tissues. Conclusion. Our findings provided new evidence that COE is an effective inhibitor of metastatic potential of SGC-7901 cells through suppression of EMT and NF-κB/Snail signal pathway. Based on these findings, COE may be considered a novel anticancer agent for the treatment of metastasis in gastric cancer.
机译：研究目的。在中国，双斜（Celastrus orbiculatus）已被用作民间药物来治疗多种疾病。在实验室中，斜Cel（Celastrus orbiculatus）（COE）的乙酸乙酯提取物显示出广泛的抗癌功能。然而，迄今为止尚未研究对胃癌细胞中COE转移机制的抑制。本研究旨在确定COE的抗转移作用是否与抑制人胃腺癌SGC-7901细胞的上皮-间质转化（EMT）有关。方法。 SGC-7901细胞的粘附，侵袭和迁移通过体外COE处理确定，分别使用Matrigel涂层板，transwell膜室和伤口愈合模型。在体内，测试了COE对胃癌裸鼠模型的生长抑制和抗转移作用，并探讨了其机制。采用免疫印迹和免疫组化方法检测EMT标志物的表达和核因子κB（NF-κB）/ Snail信号通路的表达。结果。 COE剂量依赖性地抑制了SGC-7901细胞的体外增殖，黏附，侵袭和迁移，这是通过增强E-钙粘蛋白的表达，减少N-钙粘蛋白和波形蛋白的表达来实现的。此外，COE抑制了肿瘤坏死因子-α诱导的NF-κB/ Snail信号通路的激活。此外，由于N-钙粘蛋白，波形蛋白，NF-κBp65和Snail的表达减少以及E-钙粘蛋白在肿瘤组织中的表达增加，COE有效抑制了裸鼠模型中的肿瘤生长和转移。结论。我们的发现提供了新的证据，表明COE通过抑制EMT和NF-κB/ Snail信号通路，是SGC-7901细胞转移潜能的有效抑制剂。基于这些发现，COE可被认为是治疗胃癌转移的新型抗癌药。

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