Resveratrol Inhibits Proliferation, Invasion, and Epithelial-Mesenchymal Transition by Increasing miR-200c Expression in HCT-116 Colorectal Cancer Cells

J Cell Biochem. 2017 Jun;118(6):1547-1555. doi: 10.1002/jcb.25816. Epub 2016 Dec 13.

Abstract

Objective: colorectal cancer (CRC) is one of the most common malignancies, associated with high rates of relapse. A notable challenge in treatment is low response rate to current therapies for advanced CRC. The miR-200c plays an essential role in tumor suppression by inhibiting epithelial-mesenchymal transition (EMT). Resveratrol, a natural compound found in red wine, reveals anti-cancer properties in several types of cancers such as CRC. The aim of current study was to evaluate the effects of resveratrol on proliferation, apoptosis, and invasion of HCT-116 cells and also expression of EMT-related genes in presences or absence of miR-200c.

Methods: the effect of resveratrol on viability was examined by MTT assay. LNA-anti-miR-200c transfection of HCT-116 cells was carried out in a time dependent manner. Then, the expression of miR-200c and EMT-related genes were quantified by qRT-PCR. Further, expression of EMT-related proteins, apoptosis, and invasion were analyzed by Western blot, Annexin V/PI staining and scratch test, respectively.

Results: resveratrol could significantly inhibit viability of HCT-116 cells. LNA-anti-miR-200c suppressed the endogenous miR-200c in transfected cells compared with the control. qRT-PCR and Western blot analysis of LNA-anti-miR-200c transfected cells revealed a considerable increase in vimentin and ZEB-1 expression, with a concomitant reduction in E-cadherin expression level. Migration of HCT-116 cells increased, and apoptosis significantly reduced in transfected cells. While, resveratrol could entirely reverse these changes by modulation of miR-200c expression.

Conclusion: our findings revealed a major role of resveratrol in apoptosis, invasion, and switching of EMT to MET phenotype through upregulation of miR-200c in CRC. J. Cell. Biochem. 118: 1547-1555, 2017. © 2016 Wiley Periodicals, Inc.

Keywords: COLORECTAL CANCER; EPITHELIAL-MESENCHYMAL TRANSITION; RESVERATROL; miR-200c.

MeSH terms

  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics*
  • Epithelial-Mesenchymal Transition / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • HCT116 Cells
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Resveratrol
  • Stilbenes / pharmacology*
  • Up-Regulation*

Substances

  • MIRN200 microRNA, human
  • MicroRNAs
  • Stilbenes
  • Resveratrol