Antiproliferative activity of bortezomib alone and in combination with cisplatin or docetaxel in head and neck squamous cell carcinoma cell lines

J Cancer Res Clin Oncol. 2008 Mar;134(3):323-30. doi: 10.1007/s00432-007-0287-9. Epub 2007 Aug 14.

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((R))) in squamous cell carcinoma of the head and neck (SCCHN) cell lines and examined the interaction of the drug with docetaxel (TAX) and cisplatin (CDDP).

Methods: Dose escalation studies were performed with eight squamous cell carcinoma cell lines using bortezomib alone or in combination with TAX or CDDP. Growth inhibitory and proapoptotic effects were measured quantitatively using cytohistology and western blot analysis.

Results: Bortezomib alone showed a significant antiproliferative activity in all SCCHN cell lines (P = 0.012), and the activity was further enhanced by the addition of TAX or CDDP (P </= 0.036). When the combination of bortezomib and CDDP was used, the dose of the latter could be reduced to yield the same antiproliferative effect as the cytotoxic drug alone (P < 0.012).

Conclusions: Our results indicate that bortezomib increases the cytotoxic activity of TAX and CDDP in SCCHN cell lines. In vivo and in the clinical setting, the addition of bortezomib may allow to reduce the doses of TAX or CDDP to decrease the systemic toxicity of these drugs.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Boronic Acids / pharmacology*
  • Boronic Acids / therapeutic use
  • Bortezomib
  • Carcinoma, Squamous Cell / drug therapy*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology*
  • Cisplatin / therapeutic use
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Head and Neck Neoplasms / drug therapy*
  • Humans
  • Pyrazines / pharmacology*
  • Pyrazines / therapeutic use
  • Taxoids / pharmacology*
  • Taxoids / therapeutic use

Substances

  • Antineoplastic Agents
  • Boronic Acids
  • Pyrazines
  • Taxoids
  • Docetaxel
  • Bortezomib
  • Cisplatin