Targeting estrogen receptor beta (ER?) for treatment of ovarian cancer: importance of KDM6B and SIRT1 for ER? expression and functionality.

ABSTRACT: Estrogen receptor (ER) ? has growth inhibitory and chemo drug potentiating effect on ovarian cancer cells. We studied the dependence of ER? function on the presence of KDM6B and SIRT1 in human ovarian cancer cells in vitro. Activation of ER? with the subtype-selective agonist KB9520 resulted in significant inhibition of human ovarian cancer cell growth. KB9520-activated ER? had an additive effect on growth inhibition in combination with cisplatin and paclitaxel, respectively. Loss of KDM6B expression had a negative effect on ER? function as a ligand-dependent inhibitor of ovarian cancer cell growth. In contrast, loss or inhibition of SIRT1 deacetylase activity restored ligand-activated ER? functionality. Presented data suggest that selective targeting of ER? with an agonist potentiate chemotherapy efficacy for the treatment of ovarian cancer and that downregulation or inhibition of SIRT1 may further enhance its therapeutic effect.

SUBMITTER: Pinton G 

PROVIDER: S-EPMC5833712 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature