1α,25(OH)₂D₃ Suppresses the Migration of Ovarian Cancer SKOV-3 Cells through the Inhibition of Epithelial-Mesenchymal Transition

Int J Mol Sci. 2016 Aug 19;17(8):1285. doi: 10.3390/ijms17081285.

Abstract

Ovarian cancer is the most lethal gynecological malignancy due to its high metastatic ability. Epithelial-mesenchymal transition (EMT) is essential during both follicular rupture and epithelium regeneration. However, it may also accelerate the progression of ovarian carcinomas. Experimental studies have found that 1α,25-dihydroxyvitamin-D3 [1α,25(OH)₂D₃] can inhibit the proliferation of ovarian cancer cells. In this study, we investigated whether 1α,25(OH)₂D₃ could inhibit the migration of ovarian cancer cells via regulating EMT. We established a model of transient transforming growth factor-β1(TGF-β1)-induced EMT in human ovarian adenocarcinoma cell line SKOV-3 cells. Results showed that, compared with control, 1α,25(OH)₂D₃ not only inhibited the migration and the invasion of SKOV-3 cells, but also promoted the acquisition of an epithelial phenotype of SKOV-3 cells treated with TGF-β1. We discovered that 1α,25(OH)₂D₃ increased the expression of epithelial marker E-cadherin and decreased the level of mesenchymal marker, Vimentin, which was associated with the elevated expression of VDR. Moreover, 1α,25(OH)₂D₃ reduced the expression level of transcription factors of EMT, such as slug, snail, and β-catenin. These results indicate that 1α,25(OH)₂D₃ suppresses the migration and invasion of ovarian cancer cells by inhibiting EMT, implying that 1α,25(OH)₂D₃ might be a potential therapeutic agent for the treatment of ovarian cancer.

Keywords: EMT; migration; ovarian cancer; vitamin D.

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cholecalciferol / pharmacology*
  • Epithelial-Mesenchymal Transition / drug effects*
  • Female
  • Humans
  • Ovarian Neoplasms / metabolism*
  • Transforming Growth Factor beta1 / pharmacology
  • Vimentin / pharmacology
  • Wound Healing / drug effects*
  • beta Catenin / metabolism

Substances

  • Cadherins
  • Transforming Growth Factor beta1
  • Vimentin
  • beta Catenin
  • Cholecalciferol