title: ABCC4 Decreases docetaxel and not cabazitaxel efficacy in prostate cancer cells in vitro.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Radiology and Nuclear Medicine, Department of Urology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands. aa.geldof@vumc.nl
authors: Daniela E
authors: DE
authors: Oprea-Lager
authors: Irene V
authors: IV
authors: Bijnsdorp
authors: Reindert J A
authors: RJ
authors: VAN Moorselaar
authors: Alfons J M
authors: AJ
authors: VAN DEN Eertwegh
authors: Otto S
authors: OS
authors: Hoekstra
authors: Albert A
authors: AA
authors: Geldof
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D000077143:Docetaxel; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000077143:Docetaxel; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D043823:Taxoids; C073492:ABCC4 protein, human; C552428:cabazitaxel