PDGF α receptor is a mediator for Cisplatin-induced Met expression

Eur J Pharmacol. 2013 Jan 15;699(1-3):227-32. doi: 10.1016/j.ejphar.2012.11.014. Epub 2012 Nov 29.

Abstract

For decades, platinum drugs have been the mainstay of cancer treatment. However, over time, drug resistance develops, leaving few treatment options. Here we show that platelet-derived growth factor α receptor (PDGF α receptor)-mediated signaling plays a key role in hepatocyte growth factor (HGF) receptor (c-Met) upregulation, which in turn is thought to play an important role in chemotherapy resistance. PDGF α receptor inhibition eliminates cisplatin-dependent Met expression in cervical cancer cell lines. PDGF α receptor inhibitors are widely used in clinical settings, suggesting that the clinical translation of our findings could reduce the suffering of people from drug resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Proto-Oncogene Proteins c-met / genetics*
  • Receptor, Platelet-Derived Growth Factor alpha / antagonists & inhibitors
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism*
  • Signal Transduction
  • Up-Regulation / drug effects
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-met
  • Receptor, Platelet-Derived Growth Factor alpha
  • Cisplatin