Antibiotic drug tigecycline reduces neuroblastoma cells proliferation by inhibiting Akt activation in vitro and in vivo

Tumour Biol. 2016 Jun;37(6):7615-23. doi: 10.1007/s13277-015-4613-6. Epub 2015 Dec 19.

Abstract

As the first member of glycylcycline bacteriostatic agents, tigecycline is approved as a novel expanded-spectrum antibiotic, which is clinically available. However, accumulating evidence indicated that tigecycline was provided with the potential application in cancer therapy. In this paper, tigecycline was shown to exert an anti-proliferative effect on neuroblastoma cell lines. Furthermore, it was found that tigecycline induced G1-phase cell cycle arrest instead of apoptosis by means of Akt pathway inhibition. In neuroblastoma cell lines, the Akt activator insulin-like growth factor-1 (hereafter referred to as IGF-1) reversed tigecycline-induced cell cycle arrest. Besides, tigecycline inhibited colony formation and suppressed neuroblastoma cells xenograft formation and growth. After tigecycline treatment in vivo, the Akt pathway inhibition was confirmed as well. Collectively, our data provided strong evidences that tigecycline inhibited neuroblastoma cells growth and proliferation through the Akt pathway inhibition in vitro and in vivo. In addition, these results were supported by previous studies concerning the application of tigecycline in human tumors treatment, suggesting that tigecycline might act as a potential candidate agent for neuroblastoma treatment.

Keywords: Akt activation; Cell cycle arrest; Cell proliferation; Neuroblastoma; Tigecycline.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Apoptosis / drug effects*
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Cell Proliferation / drug effects*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • Humans
  • In Vitro Techniques
  • Insulin-Like Growth Factor I / metabolism
  • Mice
  • Mice, SCID
  • Minocycline / analogs & derivatives*
  • Minocycline / pharmacology
  • Neuroblastoma / drug therapy
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects
  • Tigecycline
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Anti-Bacterial Agents
  • Biomarkers, Tumor
  • Insulin-Like Growth Factor I
  • Tigecycline
  • Proto-Oncogene Proteins c-akt
  • Minocycline