Nimotuzumab suppresses epithelial-mesenchymal transition and enhances apoptosis in low-dose UV-C treated salivary adenoid cystic carcinoma cell lines in vitro

Anticancer Drugs. 2014 Oct;25(9):1052-60. doi: 10.1097/CAD.0000000000000139.

Abstract

Salivary adenoid cystic carcinoma (SACC), which is one of the most common malignant tumors of the salivary glands, is associated with a poor long-term outcome. There are currently few therapeutic options for patients with SACC. Recent studies have shown the potential of the application of ultraviolet-C (UV-C) irradiation for the treatment of human cancer. In the present study, we investigated the effects of UV-C in the SACC cell lines SACC-83 and SACC-LM. High-dose UV-C (200 J/m) induced apoptosis and inhibited colony formation significantly. However, low-dose UV-C (10 J/m), which had little effect on apoptosis and colony formation, increased the ability of migration in SACC cells accompanied by a decrease in E-cadherin and an increase in vimentin, suggesting the occurrence of epithelial-mesenchymal transition (EMT). Low-dose UV-C (10 J/m) also resulted in upregulation of the phosphorylated forms of epidermal growth factor receptor (EGFR) and Akt (p-EGFR and p-Akt, respectively). Pretreatment with Nimotuzumab, an anti-EGFR monoclonal antibody, reversed the EMT as well as upregulation of p-EGFR/p-Akt induced by UV-C. Moreover, Nimotuzumab enhanced UV-C induced apoptosis and inhibition of colony formation. Our results indicate that EMT exerts a protective effect against apoptosis induced by low-dose UV-C. Thus, the combined application of Nimotuzumab and low-dose UV-C in vitro has an advantageous antitumor effect in SACC compared with the application of UV-C alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cadherins / metabolism
  • Carcinoma, Adenoid Cystic / pathology*
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / radiation effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Epithelial-Mesenchymal Transition / radiation effects
  • ErbB Receptors / metabolism
  • Humans
  • Oncogene Protein v-akt / metabolism
  • Phosphorylation
  • Salivary Gland Neoplasms / pathology*
  • Signal Transduction / drug effects
  • Ultraviolet Rays*
  • Vimentin / metabolism

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Cadherins
  • Vimentin
  • nimotuzumab
  • EGFR protein, human
  • ErbB Receptors
  • Oncogene Protein v-akt