Ginkgolide B Inhibits Human Bladder Cancer Cell Migration and Invasion Through MicroRNA-223-3p

Cell Physiol Biochem. 2016;39(5):1787-1794. doi: 10.1159/000447878. Epub 2016 Oct 17.


Background/aims: Ginkgolide B (GB) is currently used as an anticancer drug for treatment of some malignant cancers. However, whether it may have therapeutic effects on bladder cancer remains unknown. Here, we studied the effects of GB on bladder cancer cells.

Methods: Bladder cells were treated with different doses of GB, and the effects on ZEB1 and microRNA-223-3p (miR-223-3p) were analyzed by RT-qPCR and/or Western blot. Prediction of a regulatory relationship between miR-93 and 3'-UTR of Beclin-1 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay.

Results: We found that GB dose-dependently decreased ZEB1 protein, but not mRNA, in bladder cancer cells, resulting in suppression of cell invasion. Moreover, in bladder cancer cells, GB dose-dependently decreased the levels of miR-223-3p, which suppressed the protein translation of ZEB1 through binding to 3'-UTR of ZEB1 mRNA. Overexpression of miR-223-3p decreased ZEB1 protein, while depletion of miR-223-3p increased ZEB1 protein in bladder cancer cells.

Conclusion: GB inhibits bladder cancer cell invasiveness through suppressing ZEB1 protein translation via upregulating miR-223-3p.

MeSH terms

  • 3' Untranslated Regions
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Beclin-1 / genetics
  • Beclin-1 / metabolism
  • Binding Sites
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Ginkgolides / pharmacology*
  • Humans
  • Lactones / pharmacology*
  • Luciferases / genetics
  • Luciferases / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Protein Biosynthesis
  • Signal Transduction
  • Urinary Bladder / drug effects
  • Urinary Bladder / metabolism
  • Urinary Bladder / pathology
  • Zinc Finger E-box-Binding Homeobox 1 / genetics*
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism


  • 3' Untranslated Regions
  • Antineoplastic Agents, Phytogenic
  • BECN1 protein, human
  • Beclin-1
  • Ginkgolides
  • Lactones
  • MIRN223 microRNA, human
  • MicroRNAs
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • ginkgolide B
  • Luciferases