1,25(OH)2D3 attenuates TGF-β1/β2-induced increased migration and invasion via inhibiting epithelial-mesenchymal transition in colon cancer cells

Biochem Biophys Res Commun. 2015 Dec;468(1-2):130-5. doi: 10.1016/j.bbrc.2015.10.146. Epub 2015 Oct 30.

Abstract

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has been reported to inhibit proliferation and migration of multiple types of cancer cells. However, the mechanism underlying its anti-metastasis effect is not fully illustrated. In this study, the effect of 1,25(OH)2D3 on TGF-β1/β2-induced epithelial-mesenchymal transition (EMT) is tested in colon cancer cells. The results suggest that 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased invasion and migration of in SW-480 and HT-29 cells. 1,25(OH)2D3 also inhibited the cadherin switch in SW-480 and HT-29 cells. TGF-β1/β2-induced increased expression of EMT-related transcription factors was also inhibited by 1,25(OH)2D3. 1,25(OH)2D3 also inhibited the secretion of MMP-2 and MMP-9 and increased expression of F-actin induced by TGF-β1/β2 in SW-480 cells. Taken together, this study suggests that the suppression of EMT might be one of the mechanisms underlying the anti-metastasis effect of 1,25(OH)2D3 in colon cancer cells.

Keywords: 1,25(OH)2D3; Colon cancer; EMT; HT-29; SW-480; VDR.

MeSH terms

  • Actins / metabolism
  • Cadherins / metabolism
  • Calcitriol / pharmacology*
  • Cell Movement / drug effects
  • Colon / drug effects
  • Colon / metabolism
  • Colon / pathology*
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • Epithelial-Mesenchymal Transition / drug effects*
  • HT29 Cells
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / prevention & control*
  • Transforming Growth Factor beta1 / metabolism*
  • Transforming Growth Factor beta2 / metabolism*
  • Vitamins / pharmacology*

Substances

  • Actins
  • Cadherins
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta2
  • Vitamins
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Calcitriol