Galiellalactone inhibits the STAT3/AR signaling axis and suppresses Enzalutamide-resistant Prostate Cancer.

ABSTRACT: Most prostate cancer patients will progress to a castration-resistant state (CRPC) after androgen ablation therapy and despite the development of new potent anti-androgens, like enzalutamide (ENZ), which prolong survival in CRPC, ENZ-resistance (ENZ^R) rapidly occurs. Re-activation of the androgen receptor (AR) is a major mechanism of resistance. Interrogating our in vivo derived ENZ^R model, we discovered that transcription factor STAT3 not only displayed increased nuclear localization but also bound to and facilitated AR activity. We observed increased STAT3 S727 phosphorylation in ENZ^R cells, which has been previously reported to facilitate AR binding. Strikingly, ENZ^R cells were more sensitive to inhibition with STAT3 DNA-binding inhibitor gali

SUBMITTER: Thaper D 

PROVIDER: S-EPMC6251893 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature