A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Inhibition of bromodomain and extraterminal domain reduces growth and invasive characteristics of chemoresistant ovarian carcinoma cells
Tekijät: Majid Momeny, Haniyeh Eyvani, Farinaz Barghi, Seyed H. Ghaffari, Sepehr Javadikooshesh, Robab Hassanvand Jamadi, Fatemeh Esmaeili, Zivar Alishahi, Azam Zaghal, Davood Bashash, Fazel S. Samani, Parisa Ghaffari, Ahmad R. Dehpour, Seyyed M. Tavangar, Kamran Alimoghaddam, Ardeshir Ghavamzadeh
Julkaisuvuosi: 2018
Lehti: Anti-Cancer Drugs
Tietokannassa oleva lehden nimi: ANTI-CANCER DRUGS
Lehden akronyymi: ANTI-CANCER DRUG
Vuosikerta: 29
Numero: 10
Aloitussivu: 1011
Lopetussivu: 1020
Sivujen määrä: 10
ISSN: 0959-4973
DOI: https://doi.org/10.1097/CAD.0000000000000681
Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy worldwide. Development of chemoresistance and peritoneal dissemination are the major reasons for low survival rate in the patients. The bromodomain and extraterminal domain (BET) proteins are known as epigenetic 'readers,' and their inhibitors are novel epigenetic strategies for cancer treatment. Accumulating body of evidence indicates that epigenetic modifications have critical roles in development of EOC, and overexpression of the BET family is a key step in the induction of important oncogenes. Here, we examined the mechanistic activity of I-BET151, a pan-inhibitor of the BET family, in therapy-resistant EOC cells. Our findings showed that I-BET151 diminished cell growth, clonogenic potential, and induced apoptosis. I-BET151 inhibited cell proliferation through down-modulation of FOXM1 and its targets aurora kinase B and cyclin B1. I-BET151 attenuated migration and invasion of the EOC cells by down-regulation of epithelial-mesenchymal transition markers fibronectin, ZEB2, and N-cadherin. I-BET151 synergistically enhanced cisplatin chemosensitivity by down-regulation of survivin and Bcl-2. Our data provide insights into the mechanistic activity of I-BET151 and suggest that BET inhibition has potential as a therapeutic strategy in therapy-resistant EOC. Further in vivo investigations on the therapeutic potential of I-BET151 in EOC are warranted. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.
