Epithelial ovarian cancer (EOC) has
exhibited marginal improvement in survival rate, despite advances in
surgical debulking and chemotherapy regimens. Although the majority of
EOC patients achieve a clinical remission after induction therapy, over
80% relapse and succumb to chemoresistant disease. In this regard, it is
of paramount importance to elucidate molecular mechanisms and signaling pathways which promote therapy resistance in EOC in order to devise novel and more effective treatment strategies.

In this study, we showed that activation of nuclear factor-κB
(NF-κB) is significantly higher in therapy-resistant EOC cells compared
to chemosensitive counterparts, which was positively associated with
resistance to cisplatin, carboplatin, paclitaxel and erlotinib. Bay 11-7082, a highly selective NF-κB inhibitor, reduced cell proliferation, clonogenicity and anoikis
resistance in the therapy-resistant EOC cells and induced apoptotic
cell death. Moreover, Bay 11-7082 decreased the expression of
pro-survival, inflammatory and metastatic genes and synergistically
increased anti-proliferative efficacy of cisplatin, carboplatin,
paclitaxel and erlotinib. Altogether, these findings suggest that NF-κB
is an attractive therapeutic target in EOC to be exploited in
translational oncology and Bay 11-7082 is a potential anti-cancer drug
to overcome chemoresistance and inhibit proliferation of the EOC cells.