Fig. 1: Testosterone supplementation strongly impairs docetaxel efficacy and accumulation.

a Impact of testosterone supplementation on docetaxel treatment in tumour bearing mice (PC346C-DCC-K). Kaplan–Meier curve depicting the cumulative survival in the four treatment groups; Docetaxel (once 33 mg/kg i.v.) or placebo in castrate (DocCx n = 13 and PlacCx n = 13, respectively) or testosterone-supplemented mice (PlacTest n = 6 and DocTest n = 6, respectively). Time till progression was calculated from the day of docetaxel treatment until tumours exceeded a volume of 1500 mm³. Mice were censored when tumours did not reach 1500 mm³ in size during the maximum follow-up of 60 days. One mouse in the DocCx treatment group was euthanised due to continued weight loss after treatment. Results from the pair-wise comparison using the log-rank test are shown in the table. b Docetaxel accumulation in PC346C-DCC-K tumours obtained 3 days after treatment in castrate or testosterone-supplemented mice (DocCx n = 6 and DocTest n = 6, respectively). ***P < 0.0001. c Normalised uptake of ³H-estradiol-17β-d-glucuronide (EbG) and C¹⁴-docetaxel in Hek293T cells transiently expressing SLCO1B3, pre/coincubated with 200 µM testosterone or vehicle control. Uptake of EbG and docetaxel was normalised to uptake in SLCO1B3-expressing cells in the absence of testosterone, and EbG was used as a positive control for OATP1B3-mediated uptake. Shown are the individual normalised uptake values (n = 9) obtained from three experiments. **P < 0.01 and *P < 0.05, respectively.