| Epidemiological and experimental studies have indicated that selenium could reduce the risk of some cancers. In our present study, Methylseleninic acid (MSA) and Seleno-L-methionine (SLM) were chosen for in vitro and in vivo assays respectively. Growth inhibition and apoptosis were detected upon MSA treatment in human ESCC cell lines EC9706 and KYSE150. Selenium (SLM) could also attenuate the growth of ESCC cells in the nude mice. MSA reducedβ-catenin protein levels in a dose-and time-dependent manner, while there was no significant change observed onβ-catenin transcriptional levels. Moreover, we found MSA accelerated the degradation ofβ-catenin and activated glycogen synthase kinase 3β(GSK-3β), which could phosphorylateβ-catenin and cause its degradation. Furthermore, after MSA treatment, some targets ofβ-catenin/TCF pathway, such as c-Myc, survivin and c-Jun, were down-regulated on their mRNA and protein levels. PARP, a substrate of caspase 3 and indicator for early apoptosis, was found cleaved after MSA treatment. Bax and Bcl-2 were also dysregulated by MSA. Notably, the apoptotic phenotypes and other effects induced by MSA could be partially reversed by the overexpression of P-catenin. In addition, other mechanisms were also involved in MSA regulation, such as PI3K/AKT signaling alteration and KLF4 regulation. Overall, our data indicate the effects induced by MSA in ESCC cells may act on the inhibition ofβ-catenin/TCF pathway. |
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