Efficient Dual Treatment of the Hormone-refractory Prostate Cancer Cell Line DU145 with Cetuximab and 1,25-Dihydroxyvitamin D₃

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 G₀/G₁-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.