Efficient dual treatment of the hormone-refractory prostate cancer cell line DU145 with cetuximab and 1,25-dihydroxyvitamin D3

In Vivo. 2007 Mar-Apr;21(2):371-6.

Abstract

Background: Targeting of the epidermal growth factor receptor (EGFR) pathway is a promising treatment strategy for aggressive androgen-refractory prostate cancer (PCa). The effect of treating the androgen-resistant PCa cell line DU145 with a combination of the anti-EGFR drug cetuximab and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) was evaluated.

Materials and methods: DU145 cells were treated with 5 nM cetuximab, 100 nM 1,25(OH)2D3 or a combination of both. The effect of the treatments on cell growth, cell-cycle and apoptosis was evaluated.

Results: Single-drug treatments decreased DU145 cell growth by up to 25% and caused a 1.5-to 1.7-fold increase of apoptosis, but did not affect the cell-cycle distribution. However, dual treatment with a combination of cetuximab and 1,25(OH)2D3 inhibited DU145 cell proliferation by 40%, caused considerable cell-cycle arrest in the Go/Gl-phase, and enhanced apoptosis by 2.5-fold (compared to the control, p < 0. 0001, p <0. 006 and p <0. 0001, respectively).

Conclusion: A combination of cetuximab and 1,25(OH)2D3 efficiently suppresses hormone-resistant PCa cell growth and could provide a basis for its clinical application.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / toxicity*
  • Antibodies, Monoclonal, Humanized
  • Apoptosis / drug effects*
  • Calcitriol / pharmacology
  • Cell Cycle / drug effects
  • Cell Division / drug effects*
  • Cell Line, Tumor
  • Cetuximab
  • ErbB Receptors / drug effects
  • ErbB Receptors / physiology
  • Humans
  • Male
  • Prostatic Neoplasms

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • ErbB Receptors
  • Calcitriol
  • Cetuximab