Cetuximab inhibits growth, peritoneal dissemination, and lymph node and lung metastasis of endometrial cancer, and prolongs host survival

Int J Oncol. 2009 Oct;35(4):725-9. doi: 10.3892/ijo_00000385.

Abstract

The purpose of this study was to explore the possibility of molecular-targeted therapy with anti-epidermal growth factor receptor (EGFR) antibody (cetuximab) for endometrial cancer to develop a new treatment for advanced endometrial cancer. We analyzed EGFR protein expression and gene mutations in the human endometrial cancer cell line HEC1A, and evaluated the in vitro and in vivo effects of cetuximab on HEC1A. EGFR expression was observed in HEC1A cells, but no mutations in the EGFR gene were detected. Cetuximab inhibited HEC1A cell growth and invasion and VEGF-A production in vitro, and HECIA cell tumor growth, its peritoneal dissemination with ascites, and lymph node and lung metastasis in vivo. In addition, the antibody prolonged the survival of a mouse model of systemic metastasis. These results suggest the possibility of molecular-targeted therapy using cetuximab for endometrial cancer.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cetuximab
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / secondary
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / prevention & control*
  • Lung Neoplasms / secondary
  • Lymphatic Metastasis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mutation
  • Neoplasm Invasiveness
  • Peritoneal Neoplasms / genetics
  • Peritoneal Neoplasms / metabolism
  • Peritoneal Neoplasms / prevention & control*
  • Peritoneal Neoplasms / secondary
  • Time Factors

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • EGFR protein, human
  • ErbB Receptors
  • Cetuximab