Herb–drug interactions between androgenic Chinese herbal medicines and androgen receptor antagonist on tumor growth: Studies on two xenograft prostate cancer animal models

Our previous study revealed that Epimedii Folium (EF) and Codonopsis Radix (CNR) significantly promoted tumor growth on a subcutaneous mouse model of prostate cancer (PCa) via enhancing the mRNA and protein expressions of androgen receptor (AR), while Astragali Radix (AGR) inhibited tumor growth via suppressing the protein expression of AR. In the present study, we aimed to investigate the potential interactions between EF, CNR or AGR and AR antagonist (abiraterone acetate [ABI]) on the tumor growth using subcutaneous and orthotopic PCa mouse models. EF, CNR, AGR and ABI were intragastrically given to mice once every 2 days for 4 weeks. The pharmacokinetics of ABI were evaluated in the plasma of rats when combined with EF, CNR, or AGR. Our results demonstrated that EF or CNR could weaken the anti-tumor effects of ABI via increasing the AR expression involving activation of the PI3K/AKT and Rb/E2F pathways and decreasing the bioavailability of ABI, while AGR could enhance the anti-tumor effects of ABI through suppressing the AR expression via inhibiting the activations of PI3K/AKT and Rb/E2F pathways and increasing the bioavailability of ABI. These findings imply that cautions should be exercised when prescribing EF and CNR for PCa patients.