Tigecycline Inhibits Glioma Growth by Regulating miRNA-199b-5p-HES1-AKT Pathway

Mol Cancer Ther. 2016 Mar;15(3):421-9. doi: 10.1158/1535-7163.MCT-15-0709. Epub 2016 Jan 28.


Tigecycline is a broad-spectrum, first-in-class glycylcycline antibiotic currently used to treat complicated skin infections and community-acquired pneumonia. However, there is accumulating evidence showing that tigecycline has anticancer properties. In this study, we found tigecycline could inhibit cell proliferation by inducing cell-cycle arrest, but not apoptosis in glioma. To find the underlying mechanism of how tigecycline inhibits cell proliferation, the expression of miRNAs, which were related to regulating cell-cycle progression, was detected with miRNA assay. We found that miR-199b-5p expression was significantly increased after tigecycline treatment, and miR-199b-5p target gene HES1 was downregulated. In addition, the PI3K/AKT pathway was inhibited and p21 expression was increased. When treated with tigecycline and miR-199b-5p antagomir simultaneously in glioma cells, we found that miR-199b-5p antagomir could partly block the effects induced by tigecycline. Tigecycline effectively upregulated miR-199b-5p expression and inhibited tumor growth in the xenograft tumor model of U87 glioma cells. These results suggest that tigecycline may induce cell-cycle arrest and inhibit glioma growth by regulating miRNA-199b-5p-HES1-AKT pathway. Thus, tigecycline is a promising agent in the treatment of malignant gliomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Minocycline / analogs & derivatives*
  • Minocycline / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA Interference
  • Rats
  • Signal Transduction / drug effects*
  • Tigecycline
  • Transcription Factor HES-1 / genetics*
  • Transcription Factor HES-1 / metabolism
  • Tumor Burden


  • Antineoplastic Agents
  • MicroRNAs
  • Transcription Factor HES-1
  • mirn199 microRNA, human
  • HES1 protein, human
  • Tigecycline
  • Proto-Oncogene Proteins c-akt
  • Minocycline