EGFR inhibition prevents in vitro tumor growth of salivary adenoid cystic carcinoma

BMC Cell Biol. 2013 Mar 9:14:13. doi: 10.1186/1471-2121-14-13.

Abstract

Background: Epidermal growth factor receptor (EGFR) is involved in the development of many human malignant tumors and plays an important role in tumor growth and metastasis. Antagonists of EGFR can suppress the growth of several malignancies; however, their therapeutic effect in adenoid cystic carcinoma (ACC) is controversial.

Results: The increased proliferation of two ACC cell lines induced by EGF-treatment was reversed by nimotuzumab. Regardless of EGF stimulation, nimotuzumab-treated ACC cells were arrested in G1 phase and showed decreased expression of Ki67. In addition, EGF activated the MAPK-dependent pathway and up-regulated the expression of matrix metalloproteinase-9 and Snail, enhancing the invasive potential of an ACC cell line (ACC-M). The effects of EGF were down-regulated by nimotuzumab treatment.

Conclusions: These results suggest that nimotuzumab can inhibit the growth and invasion of ACC cells induced by EGF, probably through inactivation of ERK phosphorylation. Thus, nimotuzumab should be considered as a promising novel agent for the treatment of ACC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antineoplastic Agents / pharmacology
  • Carcinoma, Adenoid Cystic / metabolism
  • Carcinoma, Adenoid Cystic / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism*
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Ki-67 Antigen / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Phosphorylation
  • Snail Family Transcription Factors
  • Transcription Factors / metabolism
  • Up-Regulation / drug effects

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Ki-67 Antigen
  • Snail Family Transcription Factors
  • Transcription Factors
  • Epidermal Growth Factor
  • nimotuzumab
  • ErbB Receptors
  • Mitogen-Activated Protein Kinase Kinases
  • Matrix Metalloproteinase 9