Emodin Inhibits the Epithelial to Mesenchymal Transition of Epithelial Ovarian Cancer Cells via ILK/GSK-3 β/Slug Signaling Pathway

Biomed Res Int. 2016:2016:6253280. doi: 10.1155/2016/6253280. Epub 2016 Dec 20.

Abstract

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Despite the anticancer capabilities of emodin observed in many cancers, including EOC, the underlying molecular mechanism remains to be elucidated. A crucial link has been discovered between the acquisition of metastatic traits and the epithelial-mesenchymal transition (EMT). The present study aimed to determine whether emodin could inhibit the EMT of EOC cells and explore the underlying mechanism. The CCK-8 assay and transwell assay showed that emodin effectively repressed the abilities of proliferation, invasion, and migration in A2780 and SK-OV-3 cells. The Western blot showed that emodin upregulated epithelial markers (E-cadherin and Claudin) while it downregulated mesenchymal markers (N-cadherin and Vimentin) and transcription factor (Slug) in a dose-dependent fashion. After transfection of siRNA-Slug, both Slug and N-cadherin were downregulated in EOC cells while E-cadherin was upregulated, which was intensified by emodin. Besides, emodin decreased the expression of ILK, p-GSK-3β, β-catenin, and Slug. Transfection of siRNA-ILK also achieved the same effects, which was further strengthened by following emodin treatment. Nevertheless, SB216763, an inhibitor of GSK-3β, could reverse the effects of emodin except for ILK expression. These findings suggest that emodin inhibited the EMT of EOC cells via ILK/GSK-3β/Slug signaling pathway.

MeSH terms

  • Cadherins / biosynthesis
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Claudin-1 / biosynthesis
  • Emodin / administration & dosage*
  • Epithelial-Mesenchymal Transition / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glycogen Synthase Kinase 3 beta / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 beta / biosynthesis
  • Glycogen Synthase Kinase 3 beta / genetics*
  • Humans
  • Indoles / administration & dosage
  • Maleimides / administration & dosage
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / genetics
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Protein Serine-Threonine Kinases / biosynthesis
  • Protein Serine-Threonine Kinases / genetics*
  • Snail Family Transcription Factors / biosynthesis*
  • Snail Family Transcription Factors / genetics
  • beta Catenin / biosynthesis

Substances

  • CLDN1 protein, human
  • Cadherins
  • Claudin-1
  • Indoles
  • Maleimides
  • SB 216763
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • beta Catenin
  • integrin-linked kinase
  • Glycogen Synthase Kinase 3 beta
  • Protein Serine-Threonine Kinases
  • Emodin