Inhibition of bromodomain and extraterminal domain reduces growth and invasive characteristics of chemoresistant ovarian carcinoma cells
| Autor: | Haniyeh Eyvani, Farinaz Barghi, Ardeshir Ghavamzadeh, Azam Zaghal, Fazel Sahraneshin Samani, Majid Momeny, Seyed H. Ghaffari, Ahmad Reza Dehpour, Parisa Ghaffari, Davood Bashash, Seyyed Mohammad Tavangar, Fatemeh Esmaeili, Zivar Alishahi, Sepehr Javadikooshesh, Robab Hassanvand Jamadi, Kamran Alimoghaddam |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Epithelial-Mesenchymal Transition endocrine system diseases Down-Regulation Apoptosis Biology Carcinoma Ovarian Epithelial Heterocyclic Compounds 4 or More Rings Epigenesis Genetic 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor Survivin Antineoplastic Combined Chemotherapy Protocols medicine Neoplasm Humans Pharmacology (medical) Epigenetics Clonogenic assay Cyclin B1 Cell Proliferation Pharmacology Ovarian Neoplasms Cell growth Proteins Drug Synergism medicine.disease ta3122 female genital diseases and pregnancy complications Bromodomain 030104 developmental biology Oncology Drug Resistance Neoplasm 030220 oncology & carcinogenesis FOXM1 Cancer research Female Cisplatin |
| Zdroj: | Anti-cancer drugs. 29(10) |
| ISSN: | 1473-5741 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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