Metabolism of Estrogens: Turnover Differs Between Platinum-Sensitive and -Resistant High-Grade Serous Ovarian Cancer Cells.
LC-HRMS
carboplatin resistance
high-grade serous ovarian cancer
interleukin-6
metabolomics
steroid hormones
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
23 Jan 2020
23 Jan 2020
Historique:
received:
09
12
2019
revised:
09
01
2020
accepted:
21
01
2020
entrez:
26
1
2020
pubmed:
26
1
2020
medline:
26
1
2020
Statut:
epublish
Résumé
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 IC
Identifiants
pubmed: 31979221
pii: cancers12020279
doi: 10.3390/cancers12020279
pmc: PMC7072378
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Slovenian Research Agency
ID : J3-8212
Organisme : Austrian Science Fund FWF
ID : I 3417
Pays : Austria
Organisme : Austrian Science Fund
ID : I 3417-B31
Organisme : Young Researcher grant
ID : R.P.
Organisme : European Union Seventh Framework Programe OCTIPS (Ovarian Cancer Therapy - Innovative Models Prolong Survival)
ID : 279113
Déclaration de conflit d'intérêts
maximum reaction velocity
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