20.500.12556/RUL-133268 Metabolism of estrogens turnover differs between platinum-sensitive and -resistant high-grade serous ovarian cancer cells 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$_{50}$ 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. high-grade serous ovarian cancer steroid hormones metabolomics LC-HRMS carboplatin resistance interleukin-6 serozni rak jajčnika visoke stopnje steroidni hormoni metabolomika true false true Angleški jezik Slovenski jezik Članek v reviji 2021-11-19 08:40:37 2021-11-19 08:40:41 2022-09-12 04:15:33 0000-00-00 00:00:00 2020 0 0 21 str. iss. 2, art. 279 Vol. 12 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-006 2072-6694 10.3390/cancers12020279 34664665 RAZ_Poschner_Stefan_2020.pdf RAZ_Poschner_Stefan_2020.pdf 1 1D9A9078BBB02D91B5FF2E3562A146C5 bf0a59b42690f5148bfd02507a2cd4204f516c8a02bd68c5cfb150fd9330fec8 7be83ae9-490c-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=151177 https://www.mdpi.com/2072-6694/12/2/279 1 ed00067d-490b-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=151176 Medicinska fakulteta 0 0 0