Nimotuzumab Inhibits Cholangiocarcinoma Cell Metastasis via Suppression of the Epithelial-Mesenchymal Transition Process

Anticancer Res. 2017 Jul;37(7):3591-3597. doi: 10.21873/anticanres.11729.

Abstract

Background/aim: Changes in epidermal growth factor receptor (EGFR) are commonly found in cancer progression, signaling a poor outcome in patients. In the present study, we aimed to investigate whether nimotuzumab could be of benefit for cholangiocarcinoma (CCA) treatment.

Materials and methods: The expression of EGFR was explored using immunohistochemical staining in cases divided into groups with low and high expression. The effect of nimotuzumab on CCA cell growth, metastasis and the molecular mechanisms by which nimotuzumab inhibits CCA cell metastasis were evaluated.

Results: The expression of EGFR was high in 55% of patients with CCA. This was significantly correlated with a shorter survival of patients. CCA cells treated with nimotuzumab showed inhibited cell growth. Moreover, nimotuzumab inhibited CCA cell metastasis via induction of E-cadherin and suppression of zinc finger protein SNAI1 (SNAIL1), vimentin and matrix metalloproteinase 9 (MMP9) expression.

Conclusion: Nimotuzumab appears to inhibit cell metastasis via suppression of the epithelial-mesenchymal transition process. Therefore, nimotuzumab should be considered as a potential therapeutic agent against CCA.

Keywords: EGFR; EMT; Opisthorchis viverrini; cholangiocarcinoma; nimotuzumab.

MeSH terms

  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Bile Duct Neoplasms / drug therapy*
  • Bile Duct Neoplasms / metabolism
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / metabolism
  • Epithelial-Mesenchymal Transition / drug effects*
  • ErbB Receptors / metabolism
  • Humans
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Metastasis / drug therapy*
  • Signal Transduction / drug effects
  • Snail Family Transcription Factors / metabolism
  • Vimentin / metabolism

Substances

  • Antibodies, Monoclonal, Humanized
  • Cadherins
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Vimentin
  • nimotuzumab
  • ErbB Receptors
  • Matrix Metalloproteinase 9