GSK1904529A, an insulin-like growth factor-1 receptor inhibitor, inhibits glioma tumor growth, induces apoptosis and inhibits migration

Mol Med Rep. 2015 Sep;12(3):3381-3385. doi: 10.3892/mmr.2015.3869. Epub 2015 May 28.

Abstract

Malignant gliomas are the most common type of primary malignancy of the central nervous system, with a poor prognosis. The therapeutic options for malignant gliomas are limited and far from satisfactory, and novel treatment strategies are urgently required to improve the outcome of the disease. Insulin‑like growth factor (IGF)/IGF‑1 receptor (IGF‑1R) signaling pathway regulates cell proliferation, motility and survival. The dysregulation of this signaling pathway has been implicated in the development of malignant gliomas. In the present study, GSK1904529A, a small molecule inhibitor of IGF‑1R, suppressed glioma cell viability, induced glioma cell apoptosis and inhibited glioma cell migration in vitro. In addition, GSK1904529A inhibited glioma tumor growth and induced tumor cell apoptosis in vivo. In conclusion, the results of the present study suggested GSK1904529A as a promising agent for the treatment of malignant glioma.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Survival / drug effects
  • Female
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Imidazoles / pharmacology*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Pyridines / pharmacology*
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • GSK1904529A
  • Imidazoles
  • Pyridines
  • Receptor, IGF Type 1