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Erschienen in: Pathology & Oncology Research 1/2019

15.11.2017 | Original Article

Etoposide Upregulates Survival Favoring Sphingosine-1-Phosphate in Etoposide-Resistant Retinoblastoma Cells

verfasst von: Vinodh Kakkassery, S. Skosyrski, A. Lüth, B. Kleuser, M. van der Giet, R. Tate, J. Reinhard, A. Faissner, S. C. Joachim, N. Kociok

Erschienen in: Pathology & Oncology Research | Ausgabe 1/2019

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Abstract

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). 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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Metadaten
Titel
Etoposide Upregulates Survival Favoring Sphingosine-1-Phosphate in Etoposide-Resistant Retinoblastoma Cells
verfasst von
Vinodh Kakkassery
S. Skosyrski
A. Lüth
B. Kleuser
M. van der Giet
R. Tate
J. Reinhard
A. Faissner
S. C. Joachim
N. Kociok
Publikationsdatum
15.11.2017
Verlag
Springer Netherlands
Erschienen in
Pathology & Oncology Research / Ausgabe 1/2019
Print ISSN: 1219-4956
Elektronische ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-017-0360-x

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