Salinomycin repressed the epithelial-mesenchymal transition of epithelial ovarian cancer cells via downregulating Wnt/β-catenin pathway

Onco Targets Ther. 2017 Feb 28:10:1317-1325. doi: 10.2147/OTT.S126463. eCollection 2017.

Abstract

Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecological malignancies. Most patients are diagnosed in the advanced stage and have distant metastasis ultimately. Salinomycin has been demonstrated to reduce invasive capacity of multiple tumor cells. The objective of this study was to investigate the effects of salinomycin on EOC cells. The cell counting kit 8 (CCK-8) and Boyden chamber assays showed that salinomycin could effectively reduce the abilities of proliferation, migration and invasion in EOC cells. The western blot assay showed that salinomycin could increase the expression of epithelial markers (E-cadherin and Keratin) while decrease the expression of mesenchymal markers (N-cadherin and vimentin) in a dose-dependent manner. These results were ascertained by reverse transcription polymerase chain reaction (RT-PCR). Besides, salinomycin could downregulate the expression of proteins associated with the Wnt/β-catenin pathway and repress the nuclear translocation of β-catenin. It was also shown that salinomycin could reverse the aberrant activation of the canonical Wnt pathway induced by GSK-3β inhibitor (SB216763). Our results revealed that salinomycin could inhibit the proliferation, migration and invasion in EOC cells. In addition, the inhibitive effect of salinomycin on the invasive ability was mediated by repressing the epithelial-mesenchymal transition (EMT) program, which may be achieved through its inhibition of the Wnt/β-catenin pathway.

Keywords: Wnt/β-catenin pathway; epithelial ovarian cancer; epithelial–mesenchymal transition; salinomycin.