Abstract
Abstract Background: PPARγ (peroxisome proliferator-activated receptor γ) is a member of the nuclear hormone receptor that is known to be anti-neoplastic. Little is known about clinical significance in gastric cancer (GC). We aimed to evaluate the mechanism related to tumor invasion, migration and epithelial-mesenchymal transition (EMT) in GC cells and in an animal model. Methods: We controlled the expression of PPARγ and galectin-9 using siRNAs and lenti-viral constructs in human GC cells, and determined the effects of PPARγ and galectin-9 on EMT using RT-PCR, and on cell migration using transfilter assay and zebrafish xenograft model. Direct binding and interaction between PPARγ and galectin-9 were evaluated using luciferase and ChiP assays. Results: Over-expression of PPARγ was accompanied by increased galectin-9 mRNA. Enhanced expression of PPARγ either galectin-9 increased the expression of E-cadherin, decreased the expression of N-cadherin, fibronectin, snail, MMPs-1, and -9, and reduced cell invasion and migration. Silencing either PPARγ or galectin-9 decreased the expression of E-cadherin, increased the expression of N-cadherin, fibronectin, and snail, and also increased cell migration and invasion. ChiP assay showed PPARγ bound to the promoter region of galectin-9. Luciferase assay demonstrated that the galectin-9 promoter activity significantly increased in PPARγ over-expressing cells compared to empty vector-treated cells, but significantly decreased in PPARγ siRNA-treated cells compared to scRNA-treated cells. PPARγ agonist caused dose-dependent cell death in GC cells, and increased the subdiploid fraction of DNA. In the zebrafish xenograft model, the number of zebrafishes in which transplanted AGS cells were migrated to tail vein and the number of migrated cancer cells were much less in PPARγ-overexpressing GC cells than in empty vector transfected cells, respectively. Conclusions: PPARγ inhibits cell invasion, migration, and EMT through up-regulation of galectin-9 in vitro and in vivo. PPARγ could be a potential therapeutic target of GC. Citation Format: Soo-Jeong Cho, Myeong-Cherl Kook, Il Ju Choi. Peroxisome Proliferator-Activated Receptor γ inhibits cell nvasion, migration and epithelial-mesenchymal transition through up-regulating Galectin-9 in gastric cancer cells and in zebrafish xenograft model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4943. doi:10.1158/1538-7445.AM2013-4943
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call