Loading…

IL-6/IL-6R pathway is a therapeutic target in chemoresistant ovarian cancer

Introduction: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy worldwide and despite an initial response to therapeutic agents, the majority of patients have chemoresistant disease. There is no treatment strategy with proven efficacy against chemoresistant EOC and in this se...

Full description

Saved in:
Bibliographic Details
Published in:Tumori 2019-02, Vol.105 (1), p.84-91
Main Authors: Yousefi, Hassan, Momeny, Majid, Ghaffari, Seyed H., Parsanejad, Nazanin, Poursheikhani, Arash, Javadikooshesh, Sepehr, Zarrinrad, Ghazaleh, Esmaeili, Fatemeh, Alishahi, Zivar, Sabourinejad, Zahra, Sankanian, Ghazaleh, Shamsaiegahkani, Sahar, Bashash, Davood, Shahsavani, Narjes, Tavakkoly-Bazzaz, Javad, Alimoghaddam, Kamran, Ghavamzadeh, Ardeshir
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Introduction: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy worldwide and despite an initial response to therapeutic agents, the majority of patients have chemoresistant disease. There is no treatment strategy with proven efficacy against chemoresistant EOC and in this setting, overcoming therapy resistance is the key to successful treatment. Methods: This study aimed to investigate expression of interleukin-6 (IL-6) (IL-6) and IL-6 receptor (IL-6R) in a panel of the EOC cell lines. To achieve this, the expression of IL-6 and its receptor were compared in the EOC cells using quantitative reverse transcription polymerase chain reaction. MTT assay was performed to obtain chemosensitivity of the EOC cells. Results: In this report, we show that expressions of IL6 and IL6R are higher in therapy-resistant EOC cells compared to sensitive ones. Higher expression of IL6 and its receptor correlated with resistance to certain chemotherapeutic agents. Moreover, our findings showed that combination of tocilizumab (Actemra; Roche), an anti-IL-6R monoclonal antibody, with carboplatin synergistically inhibited growth and proliferation of the EOC cells and the most direct axis for IL-6 gene expression was NF-κB pathway. Conclusion: Collectively, our findings suggest that blockade of the IL-6 signaling pathway with anti-IL-6 receptor antibody tocilizumab might resensitize the chemoresistant cells to the current chemotherapeutics.
ISSN:0300-8916
2038-2529
DOI:10.1177/0300891618784790