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.
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.
Authors: Daniela E Oprea-Lager; Mitchell P van Kanten; Reindert J A van Moorselaar; Alfons J M van den Eertwegh; Peter M van de Ven; Irene V Bijnsdorp; Otto S Hoekstra; Albert A Geldof Journal: Mol Imaging Biol Date: 2015-06 Impact factor: 3.488
Authors: Oleg Mayba; Florian Gnad; Michael Peyton; Fan Zhang; Kimberly Walter; Pan Du; Melanie A Huntley; Zhaoshi Jiang; Jinfeng Liu; Peter M Haverty; Robert C Gentleman; Ruiqiang Li; John D Minna; Yingrui Li; David S Shames; Zemin Zhang Journal: Pac Symp Biocomput Date: 2014
Authors: A Janssen; C P M Verkleij; A van der Vlist; R H J Mathijssen; H J Bloemendal; R Ter Heine Journal: Br J Cancer Date: 2017-04-11 Impact factor: 7.640