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


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).


CONCLUSIONS
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.
Belochitski
Olga
O
Department of Oncology, Soroka Medical Center and Faculty of Health Sciences, Ben-Gurion University Cancer Research Center, Beer-Sheva, Israel.
Ariad
Samuel
S
Shany
Shraga
S
Fridman
Vladimir
V
Gavrilov
Vladimir
V
D000911:Antibodies, Monoclonal / Q000633:toxicity*; D061067:Antibodies, Monoclonal, Humanized; D017209:Apoptosis / Q000187:drug effects*; D002117:Calcitriol / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D000068818:Cetuximab; D066246:ErbB Receptors / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D066246:ErbB Receptors; D002117:Calcitriol; D000068818:Cetuximab