Selective inhibition of the epidermal growth factor receptor by ZD1839 decreases the growth and invasion of ovarian clear cell adenocarcinoma cells

Clin Cancer Res. 2002 Jul;8(7):2448-54.

Abstract

The mechanism that regulates the growth of ovarian clearcell adenocarcinoma (CCA) are not well understood. We investigated the role of several growth factors that bind to membrane tyrosine kinase receptors and added them to the ovarian CCA cell lines KK, RMG-1, and HAC-II to evaluate their effect on growth and cellular invasion. Epidermal growth factor and transforming growth factor-alpha significantly stimulated the growth and invasion of CCA cell lines in vitro. ZD1839, an epidermal growth factor receptor-tyrosine kinase inhibitor, decreased the growth and invasion of CCA cell lines in vitro and in vivo inhibited the growth of xenografts of the CCA cell line RMG-1. Severe combined immunodeficient mice bearing RMG-1 xenografts treated with ZD1839 survived for longer than the untreated control group. From these findings, we conclude that ZD1839 may offer a new and effective treatment for ovarian CCA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Clear Cell / drug therapy
  • Adenocarcinoma, Clear Cell / metabolism
  • Adenocarcinoma, Clear Cell / pathology*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Division / drug effects
  • Cytokines / metabolism
  • Endothelial Growth Factors / metabolism
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / metabolism
  • Female
  • Gefitinib
  • Growth Substances / metabolism
  • Humans
  • Immunoenzyme Techniques
  • In Vitro Techniques
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lymphokines / metabolism
  • Mice
  • Mice, SCID
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Phosphorylation
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Quinazolines / pharmacology*
  • Transforming Growth Factor alpha / metabolism
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Antineoplastic Agents
  • Cytokines
  • Endothelial Growth Factors
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Quinazolines
  • Transforming Growth Factor alpha
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Gefitinib