ArticleJournal of molecular medicine (Berlin, Germany)2013
Platinum-resistance in ovarian cancer cells is mediated by IL-6 secretion via the increased expression of its target cIAP-2.
Article in Journal of molecular medicine (Berlin, Germany), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Is ovarian cancer a targetable disease? A systematic review and meta-analysis and genomic data investigation.Oncotarget · 2016Pooled it
- Cell-intrinsic and tumor microenvironmental determinants of platinum resistance in epithelial ovarian cancer.Discover oncology · 2026Review
- Role of interleukin-6 in resistance to tumor therapy.Discover oncology · 2025Review
- Cell-intrinsic platinum response and associated genetic and gene expression signatures in ovarian cancer.Cancer gene therapy · 2025Article
- Interleukin-6 Modulation in Ovarian Cancer Necessitates a Targeted Strategy: From the Approved to Emerging Therapies.Cancers · 2024Review
- Novel players in the development of chemoresistance in ovarian cancer: ovarian cancer stem cells, non-coding RNA and nuclear receptors.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Focus on Trabectedin in Ovarian Cancer: What Do We Still Need to Know?Drug design, development and therapy · 2024Review
- Combining TNFR2-Expressing Tregs and IL-6 as Superior Diagnostic Biomarkers for High-Grade Serous Ovarian Cancer Masses.Cancers · 2023Article
- PFKFB3 Regulates Chemoresistance, Metastasis and StemnessFrontiers in oncology · 2022Article
- Exploring the clinical value of tumor microenvironment in platinum-resistant ovarian cancer.Seminars in cancer biology · 2021Review
- Assessment of clinical variables as predictive markers in the development and progression of colorectal cancer.Bioengineered · 2021Article
- IL-6 signaling in macrophages is required for immunotherapy-driven regression of tumors.Journal for immunotherapy of cancer · 2021Article
- Interleukin-6-mediated resistance to immunotherapy is linked to impaired myeloid cell function.International journal of cancer · 2021Article
- The Capacity of the Ovarian Cancer Tumor Microenvironment to Integrate Inflammation Signaling Conveys a Shorter Disease-free Interval.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Interaction of head and neck squamous cell carcinoma cells and mesenchymal stem cells under hypoxia and normoxia.Oncology letters · 2020Article
- Nanoantibiotics containing membrane-active human cathelicidin LL-37 or synthetic ceragenins attached to the surface of magnetic nanoparticles as novel and innovative therapeutic tools: current status and potential future applications.Journal of nanobiotechnology · 2020Review
- Prognostic and Clinical Value of Interleukin 6 and CD45Journal of immunology research · 2020Article
- Role of CC Chemokines Subfamily in the Platinum Drugs Resistance Promotion in Cancer.Frontiers in immunology · 2020Review
- Interleukin-6 as a biomarker in patients with hepatobiliary cancers.Journal of gastrointestinal oncology · 2019Article
- IL-6 mediates platinum-induced enrichment of ovarian cancer stem cells.JCI insight · 2018Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ovarian carcinoma patients are initially responsive to platinum-based therapy, but eventually become refractory to treatment due to the development of platinum chemoresistance. Elevated levels of interleukin-6 (IL-6) in the sera and ascites of these patients predict poor clinical outcome. Our goal was to analyze the interaction between cisplatin and cisplatin-resistant ovarian cancer cells, and to identify means of circumventing platinum resistance. We studied ovarian carcinoma cell lines and cells drawn from ovarian carcinoma patients. Gene array analyses were performed on ovarian carcinoma cells upon treatment with cisplatin, and the results were validated by ELISA and Western blotting (WB). Cytotoxicity assays were performed on anti-IL-6 Ab-, IL-6-, and cellular inhibitor of apoptosis 2 (cIAP-2) siRNA-treated cells, following cisplatin addition. Our results revealed a highly significant increase in IL-6 and cIAP-2 mRNA and protein levels upon treatment with cisplatin. WB analysis of cisplatin-treated cells exhibited decreased cIAP-2 expression level following anti-IL-6 Ab addition. Furthermore, IL-6 by itself, significantly increased cIAP-2 levels in ovarian carcinoma cells. Finally, cytotoxicity assays showed sensitization to cisplatin following the addition of IL-6 and cIAP-2 inhibitors. In conclusion, cisplatin treatment of ovarian carcinoma cells upregulates IL-6 and cIAP-2 levels while their inhibition significantly sensitizes them to cisplatin. Here, we present cIAP-2 as a novel inducer of platinum resistance in ovarian carcinoma cells, and suggest an axis beginning with an encounter between cisplatin and these cells, mediated sequentially by IL-6 and cIAP-2, resulting in cisplatin resistance. Consequently, we propose that combining IL-6/cIAP-2 inhibitors with cisplatin will provide new hope for ovarian carcinoma patients by improving the current treatment.
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