- Improved knowledge of retinoblastoma chemotherapy resistance is needed to raise treatment efficiency. The objective of this study was to test whether etoposide alters glucosyl-ceramide, ceramide, sphingosine, and sphingosine-1-phosphate (sphingosine-1-P) levels in parental retinoblastoma cells (WERI Rb1) or their etoposide-resistant subclones (WERI EtoR). WERI Rb1 and WERI EtoR were incubated with 400 ng/ml etoposide for 24 h. Levels of glucosyl-ceramides, ceramides, sphingosine, sphingosine-1-P were detected by Q-TOF mass spectrometry. Statistical analysis was done by ANOVA followed by Tukey post-hoc test (p < 0.05). The mRNA expression of sphingolipid pathways enzymes in WERI Rb1, WERI EtoR and four human retinoblastoma tissue samples was analyzed by quantitative real-time PCR. Pathways enzymes mRNA expression confirmed similarities of human sphingolipid metabolism in both cell lines and tissue samples, but different relative expression. Significant up-regulation of sphingosine was seen in both cell lines (p < 0.001). OnlyImproved knowledge of retinoblastoma chemotherapy resistance is needed to raise treatment efficiency. The objective of this study was to test whether etoposide alters glucosyl-ceramide, ceramide, sphingosine, and sphingosine-1-phosphate (sphingosine-1-P) levels in parental retinoblastoma cells (WERI Rb1) or their etoposide-resistant subclones (WERI EtoR). WERI Rb1 and WERI EtoR were incubated with 400 ng/ml etoposide for 24 h. Levels of glucosyl-ceramides, ceramides, sphingosine, sphingosine-1-P were detected by Q-TOF mass spectrometry. Statistical analysis was done by ANOVA followed by Tukey post-hoc test (p < 0.05). The mRNA expression of sphingolipid pathways enzymes in WERI Rb1, WERI EtoR and four human retinoblastoma tissue samples was analyzed by quantitative real-time PCR. Pathways enzymes mRNA expression confirmed similarities of human sphingolipid metabolism in both cell lines and tissue samples, but different relative expression. Significant up-regulation of sphingosine was seen in both cell lines (p < 0.001). Only sphingosine-1-P up-regulation was significantly increased in WERI EtoR (p < 0.01), but not in WERI Rb1 (p > 0.2). Both cell lines upregulate pro-apoptotic sphingosine after etoposide incubation, but only WERI EtoR produces additional survival favorable sphingosine-1-P. These data may suggest a role of sphingosine-1-P in retinoblastoma chemotherapy resistance, although this seems not to be the only resistance mechanism.…
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MetadatenVerfasserangaben: | Vinodh KakkasseryORCiDGND, S. Skosyrski, A. Lüth, Burkhard KleuserORCiDGND, Maria van der GietGND, R. Tate, J. Reinhard, Andreas FaissnerORCiDGND, Stephanie Christine JoachimGND, N. Kociok |
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DOI: | https://doi.org/10.1007/s12253-017-0360-x |
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ISSN: | 1219-4956 |
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ISSN: | 1532-2807 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/29143233 |
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Titel des übergeordneten Werks (Englisch): | Pathology & Oncology Research |
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Verlag: | Springer |
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Verlagsort: | Dordrecht |
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Publikationstyp: | Wissenschaftlicher Artikel |
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Sprache: | Englisch |
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Datum der Erstveröffentlichung: | 15.11.2017 |
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Erscheinungsjahr: | 2017 |
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Datum der Freischaltung: | 25.05.2021 |
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Freies Schlagwort / Tag: | Chemotherapy resistance; Retinoblastoma; Sphingosine-1-phosphate |
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Band: | 25 |
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Ausgabe: | 1 |
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Seitenanzahl: | 9 |
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Erste Seite: | 391 |
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Letzte Seite: | 399 |
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Fördernde Institution: | Jackstadt-Stiftung [S 134-10.063]; Deutsche Forschungsgemeinschaft DFGGerman Research Foundation (DFG) [KL988/4-4] |
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Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
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DDC-Klassifikation: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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