turnover differs between platinum-sensitive and -resistant high-grade serous ovarian cancer cells
Stefan Poschner (Author), Judith Wackerlig (Author), Dan Cacsire Castillo-Tong (Author), Andrea Wolf (Author), Isabel von der Decken (Author), Tea Lanišnik-Rižner (Author), Renata Pavlič (Author), Anastasia Meshcheryakova (Author)

Abstract

High-grade serous ovarian cancer (HGSOC) is currently treated with cytoreductive surgery and platinum-based chemotherapy. The majority of patients show a primary response; however, many rapidly develop drug resistance. Antiestrogens have been studied as low toxic treatment options for HGSOC, with higher response rates in platinum-sensitive cases. Mechanisms for this difference in response remain unknown. Therefore, the present study investigated the impact of platinum resistance on steroid metabolism in six established HGSOC cell lines sensitive and resistant against carboplatin using a high-resolution mass spectrometry assay to simultaneously quantify the ten main steroids of the estrogenic metabolic pathway. An up to 60-fold higher formation of steroid hormones and their sulfated or glucuronidated metabolites was observed in carboplatin-sensitive cells, which was reversible by treatment with interleukin-6 (IL-6). Conversely, treatment of carboplatin-resistant cells expressing high levels of endogenous IL-6 with the monoclonal anti-IL-6R antibody tocilizumab changed their status to "platinum-sensitive", exhibiting a decreased IC50 value for carboplatin, decreased growth, and significantly higher estrogen metabolism. Analysis of these metabolic differences could help to detect platinum resistance in HGSOC patients earlier, there by allowing more efficient interventions.

Keywords

serozni rak jajčnika visoke stopnje;steroidni hormoni;metabolomics;high-grade serous ovarian cancer;steroid hormones;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL MF - Faculty of Medicine
UDC: 616-006
COBISS: 34664665 Link will open in a new window
ISSN: 2072-6694
Views: 196
Downloads: 76
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Other data

Secondary language: Slovenian
Secondary keywords: serozni rak jajčnika visoke stopnje;steroidni hormoni;metabolomika;
Type (COBISS): Article
Pages: str. 1-21
Issue: ǂVol. ǂ12
Chronology: 2020
DOI: 10.3390/cancers12020279
ID: 13981588