Inhibition of androgen/AR signaling inhibits diethylnitrosamine (DEN) induced tumour initiation and remodels liver immune cell networks.

摘要: A promotional role for androgen receptor (AR) signaling in hepatocellular carcinogenesis is emerging. In pre-clinical models, including diethylnitrosamine- (DEN-) induced carcinoma (HCC), anti-androgen therapies delay hepatocarcinogenesis. However, pharmacologic therapy advanced HCC patients fails, suggesting that AR plays a onset. This study aims to characterize expression and function throughout DEN-induced liver inflammation evaluate the efficacy of prophylactic antagonism prevent We demonstrate with enzalutamide inhibits carcinogenesis. With treatment, we observe decreased CYP2E1 expression, reducing DEN-induced hepatocyte death and DNA ethyl-adducts. protein analyses show DEN causes an initial upregulation portal fibroblasts leukocytes, but not hepatocytes, hepatocyte-autonomous essential Ablating by surgical castration reduced pre-carcinogen Kupffer cell populations did alter DEN-mediated immune recruitment nor expression. this study, identified interventions modulate mutagenic DNA adducts, tumour initiation, composition. Additionally, find hepatocytes present during required early