Cetuximab enhances the efficacy of bortezomib in squamous cell carcinoma cell lines

J Cancer Res Clin Oncol. 2009 Mar;135(3):387-93. doi: 10.1007/s00432-008-0477-0. Epub 2008 Oct 1.

Abstract

Purpose: Proteasome inhibition has been shown to be effective in multiple myeloma and solid tumor models. In this in vitro study, we investigated the antitumor effect of bortezomib (Velcade) in combination with cetuximab in squamous cell carcinoma cell lines (SCC).

Methods: Dose-escalation studies were performed in five squamous cell carcinoma cell lines using bortezomib or cetuximab alone or in combination. Cell survival and growth inhibition were measured quantitatively using an MTT and LDH assay.

Results: Bortezomib alone showed a significant antiproliferative activity in all SCC cell lines (P < 0.042), and the activity was further significantly enhanced by the addition of cetuximab (P < 0.043).

Conclusions: Our results indicate that cetuximab increases the cytotoxic activity of bortezomib in SCC cell lines. Combination therapy of SCC with bortezomib and cetuximab might be less toxic than conventional drug regimens used in the treatment of these tumors.

MeSH terms

  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Boronic Acids / administration & dosage
  • Boronic Acids / therapeutic use*
  • Bortezomib
  • Carcinoma, Squamous Cell / drug therapy*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cetuximab
  • Esophageal Neoplasms / drug therapy
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / physiology
  • Humans
  • Mouth Neoplasms / drug therapy
  • Multiple Myeloma / drug therapy
  • Pyrazines / administration & dosage
  • Pyrazines / therapeutic use*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Boronic Acids
  • Pyrazines
  • Bortezomib
  • Cetuximab