Gefitinib causes growth arrest and inhibition of metastasis in human chondrosarcoma cells

J BUON. 2015 May-Jun;20(3):894-901.

Abstract

Purpose: Chondrosarcomas are primary malignant cartilage-forming tumors of bone which are not responsive either to chemotherapy or radiation treatment and display potent capacity to invade locally and cause distant metastasis. Epidermal growth factor receptor (EGFR) pathway plays an important role in the development and progression of many cancers. However, the effect of EGFR inhibitor gefitinib on cell growth and metastasis in human chondrosarcoma cells is largely unknown.

Methods: Features of the protein expression of EGFR in 3 human chondrosarcoma cell lines JJ2012, SW1353 and OUMS27 were analyzed. The inhibitory effects of EGFR inhibitor gefitinib on cell proliferation, cell cycle and metastasis were assessed by using MTS, flow cytometry and migration assays, respectively. The expression of metastasis-related proteins was evaluated by western blotting.

Results: All the three human chondrosarcoma cell lines expressed EGFR protein. Gefitinib significantly inhibited the growth, induced cell cycle arrest and decreased the migra- tion ability of human chondrosarcoma cells. In addition, gefitinib also reduced the expression of metastasis-related proteins, basic fibroblast growth factor (bFGF), matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9).

Conclusions: The discovery that gefitinib inhibited the proliferation and reduced the metastatic capacity of chondrosarcoma cells may help increase the understanding of the mechanism underlying human chondrosarcoma growth and metastasis. Thus, gefitinib may represent a promising agent for controlling chondrosarcoma proliferation and metastasis.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology*
  • Cell Cycle Checkpoints / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Chondrosarcoma / metabolism
  • Chondrosarcoma / pathology*
  • Dose-Response Relationship, Drug
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Fibroblast Growth Factor 2 / metabolism
  • Gefitinib
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness
  • Protein Kinase Inhibitors / pharmacology*
  • Quinazolines / pharmacology*
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinazolines
  • Fibroblast Growth Factor 2
  • EGFR protein, human
  • ErbB Receptors
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • Gefitinib