Blockade of Nuclear Factor-Κb (Nf-Κb) Pathway Inhibits Growth and Induces Apoptosis in Chemoresistant Ovarian Carcinoma Cells Publisher Pubmed



Momeny M¹ ; Yousefi H² ; Eyvani H³ ; Moghaddaskho F³ ; Salehi A⁴ ; Esmaeili F² ; Alishahi Z² ; Barghi F³ ; Vaezijoze S³ ; Shamsaiegahkani S³ ; Zarrinrad G³ ; Sankanian G³ ; Sabourinejad Z⁵ ; Hamzehlou S² Show All Authors Show Affiliations
Source: International Journal of Biochemistry and Cell Biology Published:2018

Abstract

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. © 2018 Elsevier Ltd