Introduction Ovarian cancer stem/progenitor cells (OVCA-CSPCs) are considered cancer promoter for their capacity of unlimited self-renewal and drug resistance. Androgen receptor (AR) belongs to nuclear receptor superfamily, which activation through binding with androgens. AR has been suggested to play role in OVCA development.

Methods Side population, sphere formation assay, CD133 expression were used to analyze the effect of AR in ovarian teratocarcinoma cell line (OVTC) PA1 CSPCs. Paclitaxel sensitivity EOC cells using AR cDNA or shRNA and the association of AR with the outcomes of EOC patients was evaluated using immunohistochemistry and web-based bioinformatics survival analyses. The molecular mechanism of the paclitaxel-AR/AhR-ABCG2 regulatory axis was delineated using promoter reporter and ChIP assay. Lastly, an AR degradation enhancer (ASC-J9) was used to test the translational potential of targeting AR to decrease paclitaxel resistance in EOC.

Results In the study, a ligand-independent AR function to enriche CSPCs via facilitated self-renewal in PA1 was demonstrated. On the other hand, The AR expression is linked to SC-EOC of taxel treatment modality to poor prognosis. Paclitaxel treatment could turn on AR tranactivation function in vitro, of which explained the paclitaxel resistance in molecular aspect. For the translational approach, the ASC-J9 (AR degradation enhancer) treatment could resensitize paclitaxel-resistance SC-EOC in vitro and in vivo. Therefore, the utilization of ASC-J9 for OVCA therapy is vivid in the future.

Conclusion/Implications This study summarized the roles of AR play in OVCA disease development in cellular and molecular levels and illustrated the mode-of-action for ASC-J9 pharmaceutical development.