RESUMO
Aberrant activation of ß-catenin signaling due to low expression of miR200a is found in gastric carcinoma (GC) tissues promoting GC evolution. Toosendanin (TSN) has exhibited antitumor effects on various human cancer cells, but its influence on GC is largely unidentified. The potential roles of TSN on GC cells were examined and it was found that TSN inhibited growth, migration, invasion and TGFß1-induced epithelial-mesenchymal transition (EMT) and induced cell cycle arrest and apoptosis in SGC7901 cells which were most sensitive to TSN among various GC cell lines. TSN also inactivated ß-catenin pathway in SGC7901 cells and the above effects were reversed following induction of ß-catenin overexpression. Moreover, TSN facilitated the level of miR200a which targets ß-catenin and miR200a silencing attenuated the antitumor effects of TSN on SGC7901 cells. Nonetheless, knockdown of miR200a did not relieve the suppressive effects of TSN on pAKT, pERK and pGSK3ß which were upstream regulators of ß-catenin. In addition, TSN administration inhibited growth and liver metastasis of orthotopically implanted SGC7901 tumors in vivo through miR200amediated ß-catenin pathway. Our data suggest that TSN may suppress oncogenic phenotypes of human GC cells partly via miR200a/ß-catenin axis. Hence, TSN may have a promising chemotherapeutic activity for GC therapy.