title: Sodium Selenite Inhibits Proliferation of Gastric Cancer Cells by Inducing SBP1 Expression.
abstract: Selenium is an essential trace element with an inhibitory effect on many types of human cancers, including gastric cancer. Selenium-binding protein 1 (SBP1) has been shown as a possible mediator of selenium's anti-cancer functions. Indeed, SBP1 was downregulated in gastric cancer, which is related with poor prognosis. However, the molecular mechanisms underlying the anti-tumor effects of SBP1 remain poorly understood. In this study, we aimed to assess the effects of selenium and/or SBP1 on the proliferation of gastric cancer cells. We used SGC7901 and N87 human gastric cancer cell lines and nude mice carrying subcutaneously implanted SGC7901 cells. Treatment with sodium selenite for 48 h caused the inhibition of cell proliferation and the increase in apoptosis of SGC7901 and N87 cells. Furthermore, sodium selenite increased the expression level of SBP1 and decreased the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and the Wnt pathway components and its downstream targets, including β-catenin, GSK-3β, c-myc and cyclinD1 in these cell lines. However, these effects of sodium selenite were attenuated in SGC7901 and N87 cells by knockdown of SBP1 expression. Thus, the sodium selenite-induced SBP1 expression is associated with the inhibition of cell proliferation and with the induced apoptosis. Importantly, sodium selenite treatment retarded the growth of the transplanted SGC7901 cells in nude mice, with the induction of SBP1 expression, which was associated with the decrease of Nrf2 expression and the inactivation of the Wnt/β-catenin signaling pathway. We suggest that sodium selenite may have a potential application in gastric cancer treatment.
authors.affiliation: Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University.
authors.forename: Jianzhuang
authors.initials: J
authors.lastname: Gong
authors.forename: Li
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D055785:Gene Knockdown Techniques; D020868:Gene Silencing / Q000187:drug effects; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D051137:Selenium-Binding Proteins / Q000378:metabolism*; D018038:Sodium Selenite / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D060449:Wnt Signaling Pathway / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495175:SELENBP1 protein, human; D051137:Selenium-Binding Proteins; D018038:Sodium Selenite