Blockade of nuclear factor-κB (NF-κB) pathway inhibits growth and induces apoptosis in chemoresistant ovarian carcinoma cells

• Published in: The international journal of biochemistry & cell biology Vol. 99; pp. 1 - 9
• Main Authors: Momeny, Majid, Yousefi, Hassan, Eyvani, Haniyeh, Moghaddaskho, Farima, Salehi, Ali, Esmaeili, Fatemeh, Alishahi, Zivar, Barghi, Farinaz, Vaezijoze, Somaye, Shamsaiegahkani, Sahar, Zarrinrad, Ghazaleh, Sankanian, Ghazaleh, Sabourinejad, Zahra, Hamzehlou, Sepideh, Bashash, Davood, Aboutorabi, Elaheh S., Ghaffari, Parisa, Dehpour, Ahmad R., Tavangar, Seyyed M., Tavakkoly-Bazzaz, Javad, Alimoghaddam, Kamran, Ghavamzadeh, Ardeshir, Ghaffari, Seyed H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-06-2018
• Subjects: Bay 11-7082; Epithelial ovarian cancer; NF-κB signaling pathway; Therapy resistance; Bay 11-7082; Therapy resistance; Epithelial ovarian cancer; NF-κB signaling pathway
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2018.03.015

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.