Ursolic Acid Inhibits Epithelial-Mesenchymal Transition through the Axl/NF-κB Pathway in Gastric Cancer Cells

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.

(1) In vitro experiments: 25μmol/L and 50μmol/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-κB, and p-NF-κB. (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.

(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-IKKα/β, and p-NF-κB in BGC-823 and MGC-803 cells. (4) UA distinctly decreased the expressions of N-Cadherin, Snail, p-Axl, and p-IKKα/β in gastric cancer xenograft model rats.

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-κB signaling pathway.