BACKGROUND: This study aimed to investigate cabazitaxel efficacy in a model for docetaxel-resistant prostate cancer cells and to evaluate the involvement of ATP-cassette binding protein 4 (ABCC4) with regard to multidrug resistance.
MATERIALS AND METHODS: Docetaxel and cabazitaxel sensitivity was measured in PC3 and R3327-MATLyLu (MLL) cell lines, using the sulforhodamine B (SRB) assay. ABCC4 expression was examined by western blotting and its functional involvement in drug sensitivity by blocking with MK571 inhibitor.
RESULTS: The docetaxel-resistant MLL cells (4.5-fold compared to cabazitaxel; p< 0.001) were shown to express high levels of ABCC4, while non-resistant PC3 cells had no detectable ABCC4 expression. Functional inhibition of ABCC4 in MLL cells resulted in a two-fold decrease in effective concentration of docetaxel and had no effect on toxicity of cabazitaxel.
CONCLUSION: Cabazitaxel showed an improved therapeutic efficacy over docetaxel in ABCC4-expressing prostate cancer cells. ABCC4 appears to be an important determinant of docetaxel resistance, since its inhibition almost completely reversed resistance.
Written by:
Oprea-Lager DE, Bijnsdorp IV, VAN Moorselaar RJ, VAN DEN Eertwegh AJ, Hoekstra OS, Geldof AA. Are you the author?
Department of Radiology and Nuclear Medicine, Department of Urology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands.
Reference: Anticancer Res. 2013 Feb;33(2):387-91.
PubMed Abstract
PMID: 23393328
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