Ursolic Acid Inhibits Epithelial-Mesenchymal Transition through the Axl/NF-B Pathway in Gastric Cancer Cells
Ursolic Acid Inhibits Epithelial-Mesenchymal Transition through the Axl/NF-B Pathway in Gastric Cancer Cells
复制标题
熊果酸通过 Axl/NF-κB 通路抑制胃癌细胞的上皮间质转化
DOI：
10.1155/2019/2474805
复制
发表时间：
2019-01-01
影响因子：
--
通讯作者：
Shen, Li
中科院分区：
文献类型：
--
作者：
Li, Jinxia;Dai, Chunyan;Shen, Li
背景熊果酸（Ursolic acid，UA）是一种抗肿瘤中药成分，本研究旨在观察UA对胃癌上皮间质转化（epithelial-mesenchymal transition，EMT）的影响。方法. (1)体外实验：25 mol/L和50 mol/L UA作用于BGC-823、AGS、MGC-803和HGC-27细胞，MTT法检测细胞增殖，Transwell法检测细胞迁移，流式细胞术检测细胞凋亡。Western blot检测N-Cadherin、Vimentin、Snail、Twist、Axl、p-Axl、IKK、p-IKK、NF-B、p-NF-B的表达。(2)体内实验：10只BALB/c-nu小鼠建立胃癌移植瘤模型。5例口服UA 4周，5例口服生理盐水。免疫组化法检测N-Cadherin、Snail的表达; Western blot法检测N-Cadherin、Snail、Twist、Axl、p-Axl、IKK、p-IKK的表达。结果(1)UA对BGC-823和HGC-27细胞的增殖有明显的抑制作用，且呈剂量依赖性。(2)UA抑制BGC-823、AGS和MGC-803细胞的迁移，同时诱导BGC-823细胞凋亡。(3)UA可显著降低BGC-823和MGC-803细胞N-Cadherin、Vimentin、Snail、Twist p-Axl、p-IKK/、p-NF-B的表达。(4)UA可明显降低胃癌移植瘤模型大鼠N-Cadherin、Snail、p-Axl、p-IKK/的表达。结论UA能有效抑制胃癌细胞的增殖和迁移，并诱导胃癌细胞凋亡。UA的抗肿瘤作用是通过抑制EMT来实现的，其机制可能与调节Axl/NF-B信号通路有关。
Background. Ursolic acid (UA) is an antitumor component derived from Chinese herbal medicine; this study is to observe the effects of UA on epithelial-mesenchymal transition (EMT) in gastric cancer. Methods. (1) In vitro experiments: 25mol/L and 50mol/L UA were applied to BGC-823, AGS, MGC-803, and HGC-27 cells; MTT staining, Transwell assay, and flow cytometry were used to assess cell proliferation, cell migration, and apoptosis, respectively. Western blot was performed to detect the expressions of N-Cadherin, Vimentin, Snail, Twist, Axl, p-Axl, IKK, p-IKK, NF-B, and p-NF-B. (2) In vivo experiments: Ten BALB/c-nu mice were used to establish gastric cancer xenograft model. Five were orally given UA for 4 weeks and five were given normal saline. Expressions of N-Cadherin and Snail were examined by immunohistochemical assay; expressions of N-Cadherin, Snail, Twist, Axl, p-Axl, IKK, and p-IKK were detected by Western blot. Results. (1) UA inhibited cell proliferation in BGC-823 and HGC-27 cells in dose-dependent manners. (2) UA inhibited cell migration in BGC-823, AGS, and MGC-803 cells while inducing apoptosis in BGC-823 cells. (3) UA significantly decreased the expressions of N-Cadherin, Vimentin, Snail, Twist p-Axl, p-IKK/, and p-NF-B in BGC-823 and MGC-803 cells. (4) UA distinctly decreased the expressions of N-Cadherin, Snail, p-Axl, and p-IKK/ in gastric cancer xenograft model rats. Conclusion. UA can effectively inhibit the proliferation and migration and induce apoptosis of gastric cancer cells. The antitumor effect of UA is conducted by EMT inhibition, which may be associated with the regulation of Axl/NF-B signaling pathway.