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

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

*Corresponding author for this work


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  0.2). 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.
Original languageEnglish
JournalPathology and Oncology Research
Issue number1
Pages (from-to)391-399
Number of pages9
Publication statusPublished - 15.01.2019

Research Areas and Centers

  • Research Area: Luebeck Integrated Oncology Network (LION)


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