Reference - Detail
|Author||Tamura F, Sato Y, Hirakawa M, Yoshida M, Ono M, Osuga T, Okagawa Y, Uemura N, Arihara Y, Murase K, Kawano Y, Iyama S, Takada K, Hayashi T, Sato T, Miyanishi K, Kobune M, Takimoto R, Kato J.|
|Title||RNAi-mediated gene silencing of ST6GalNAc I suppresses the metastatic potential in gastric cancer cells.|
BACKGROUND:ST6GalNAc I is a sialyltransferase controlling the expression of sialyl-Tn antigen (STn), which is overexpressed in several epithelial cancers, including gastric cancer, and is highly correlated with cancer metastasis. However, the functional contribution of ST6GalNAc I to development or progression of gastric cancer remains unclear. In this study, we investigated the effects of suppression of ST6GalNAc I on gastric cancer in vitro and in vivo.
METHODS:Gastric cancer cell lines were transfected with ST6GalNAc I siRNA and were examined by cell proliferation, migration, and invasion assays. We also evaluated the effect of ST6GalNAc I siRNA treatment in a peritoneal dissemination mouse model. The differences in mRNA levels of selected signaling molecules were analyzed by polymerase chain reaction (PCR) arrays associated with tumor metastasis in MKN45 cells. The signal transducer and activator of transcription 5b (STAT5b) signaling pathways that reportedly regulate the insulin-like growth factor-1 (IGF-1) were analyzed by Western blot.
RESULTS:ST6GalNAc I siRNA inhibited gastric cancer cell growth, migration, and invasion in vitro. Furthermore, intraperitoneal administration of ST6GalNAc I siRNA- liposome significantly inhibited peritoneal dissemination and prolonged the survival of xenograft model mice with peritoneal dissemination of gastric cancer. PCR array confirmed that suppression of ST6GalNAc I caused a significant reduction in expression of IGF-1 mRNA. Decreased IGF-1 expression in MKN45 cells treated with ST6GalNAc I siRNA was accompanied by reduced phosphorylation of STAT5b.
CONCLUSION:ST6GalNAc I may regulate the gene expression of IGF-1 through STAT5b activation in gastric cancer cells and may be a potential target for treatment of metastasizing gastric cancer.
|MeSH||Animals Antigens, Tumor-Associated, Carbohydrate / metabolism Cell Line, Tumor Cell Movement / genetics Female Gene Expression Regulation, Enzymologic Gene Silencing Humans Insulin-Like Growth Factor I / genetics Insulin-Like Growth Factor I / metabolism Mice, Inbred BALB C Peritoneal Neoplasms / secondary RNA Interference* STAT5 Transcription Factor / metabolism Sialyltransferases / genetics* Sialyltransferases / metabolism Stomach Neoplasms / enzymology* Stomach Neoplasms / mortality Stomach Neoplasms / pathology* Xenograft Model Antitumor Assays|
|WOS Category||ONCOLOGY GASTROENTEROLOGY & HEPATOLOGY|
|Human and Animal Cells|