Blockade of nuclear factor-κB (NF-κB) pathway inhibits growth and induces apoptosis in chemoresistant ovarian carcinoma cells
| Autor: | Farinaz Barghi, Fatemeh Esmaeili, Seyed H. Ghaffari, Somaye Vaezijoze, Ardeshir Ghavamzadeh, Ghazaleh Zarrinrad, Davood Bashash, Seyyed Mohammad Tavangar, Ahmad Reza Dehpour, Zahra Sabourinejad, Elaheh S. Aboutorabi, Ghazaleh Sankanian, Kamran Alimoghaddam, Hassan Yousefi, Majid Momeny, Parisa Ghaffari, Haniyeh Eyvani, Sepideh Hamzehlou, Sahar Shamsaiegahkani, Javad Tavakkoly-Bazzaz, Zivar Alishahi, Ali Salehi, Farima Moghaddaskho |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
endocrine system diseases medicine.medical_treatment Antineoplastic Agents Apoptosis ta3111 Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Tumor Cells Cultured medicine Humans Cell Proliferation Ovarian Neoplasms Cisplatin Chemotherapy business.industry Cell growth NF-kappa B Cell Biology Anoikis Debulking female genital diseases and pregnancy complications Carboplatin Gene Expression Regulation Neoplastic 030104 developmental biology Paclitaxel chemistry Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research Female Erlotinib business medicine.drug |
| Zdroj: | International Journal of Biochemistry and Cell Biology. 99:1-9 |
| ISSN: | 1357-2725 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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