XXXX increases the radiosensitivity and reverses epithelial-to-mesenchymal transition of radioresistant @entity418 cell line KYSE-150R.

@entity1 @entity5907 @entity18142 @entity5962 @entity1721 @entity4910 @entity3546 @entity418 @entity9459 @entity15711
BACKGROUND: Acquired radioresistance has significantly compromised the efficacy of radiotherapy for @entity418 . The purpose of this study is to investigate the roles of epithelial-mesenchymal transition (EMT) and the Wnt/ @entity3546 signaling pathway in the acquirement of radioresistance during the radiation treatment of @entity418 . METHODS: We previously established a radioresistant cell line ( @entity1 R) from the @entity1 cell line (a @entity1 cell line model for @entity1721 ) with a gradient cumulative irradiation dose. In this study, the expression of EMT phenotypes and the Wnt/ @entity3546 signaling pathway proteins were examined by real-time PCR, western blot and immunofluorescence in the @entity1 R cells. The @entity1 R cells were then treated with a @entity3546 / @entity5907 inhibitor @entity15711 . The expressions of nuclear and cytoplasmic @entity3546 and EMT markers in @entity1 R cells were assessed at both mRNA and protein level after @entity15711 treatment. The radiosensitization effect of @entity15711 on KYSE-150R was evaluated by CCK8 analysis and a colony forming assay. DNA repair capacities was detected by the neutral comet assays. RESULTS: @entity1 R cell line displayed obvious radiation resistance and had a stable genetic ability. EMT phenotype was presented in the @entity1 R cells with decreased @entity5962 and increased snail and twist expressions. The up-regulated expressions of Wnt/ @entity3546 signaling pathway proteins ( @entity18142 , FZD1-4, @entity9459 , @entity3546 and @entity4910 ), the increased phosphorylation of @entity9459 , and the decreased phosphorylation of @entity3546 were observed in @entity1 R cells compared with @entity1 cells, implicating the activation of the Wnt pathway in @entity1 R cells. The expression of nuclear @entity3546 and nuclear translocation of @entity3546 from the cytoplasm was decreased after @entity15711 treatment. @entity15711 also reversed EMT phenotypes by increasing @entity5962 expression. The cell proliferation rates of KYSE-150R were dose-dependent and the radiation survival fraction was significantly decreased upon @entity15711 treatment. Neutral comet assays indicated that @entity15711 impairs DNA double stranded break repair in @entity1 R cells. CONCLUSIONS: Acquisition of radioresistance and EMT in @entity418 cells is associated with the activation of the Wnt/ @entity3546 pathway. EMT phenotypes can be reduced and the radiosensitivity of @entity418 cells can be enhanced by inhibiting the Wnt/ @entity3546 pathway with @entity15711 treatment.
