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Updated: Feb 7, 2026

Enrichment for Chemoresistant Ovarian Cancer Stem Cells from Human Cell Lines
Published on: September 10, 2014
IL-6/IL-6R pathway is a therapeutic target in chemoresistant ovarian cancer
Hassan Yousefi1,2, Majid Momeny1, Seyed H Ghaffari1
11 Hematology/Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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.
Insights
Interleukin-6 (IL-6) signaling drives chemoresistance in epithelial ovarian cancer (EOC). Blocking IL-6 with tocilizumab resensitizes resistant EOC cells to chemotherapy, offering a new treatment strategy.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Epithelial ovarian cancer (EOC) is a leading cause of cancer death globally.
- Most EOC patients develop chemoresistant disease, necessitating novel therapeutic strategies.
- Overcoming therapy resistance is critical for improving EOC patient outcomes.
Purpose of the Study:
- To investigate the expression of interleukin-6 (IL-6) and its receptor (IL-6R) in EOC cell lines.
- To correlate IL-6/IL-6R expression with chemosensitivity in EOC.
- To evaluate the therapeutic potential of targeting the IL-6 pathway in chemoresistant EOC.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction (RT-qPCR) to measure IL-6 and IL-6R expression.
- MTT assay to determine chemosensitivity of EOC cell lines.
- Treatment of EOC cells with tocilizumab (anti-IL-6R antibody) and carboplatin.
Main Results:
- Higher IL-6 and IL-6R expression was observed in therapy-resistant EOC cells compared to sensitive cells.
- Elevated IL-6/IL-6R levels correlated with resistance to specific chemotherapeutic agents.
- Combination therapy with tocilizumab and carboplatin synergistically inhibited EOC cell growth and proliferation.
- The NF-κB pathway was identified as a key regulator of IL-6 gene expression.
Conclusions:
- IL-6 signaling blockade using tocilizumab may resensitize chemoresistant EOC cells to existing chemotherapeutics.
- Targeting the IL-6 pathway represents a promising strategy to overcome treatment resistance in EOC.
- Further clinical investigation of IL-6 pathway inhibitors in EOC is warranted.
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