Sorafenib treatment and modulation of the sphingolipid pathway affect proliferation and viability of hepatocellular carcinoma In vitro
- Hepatocellular carcinoma (HCC) shows a remarkable heterogeneity and is recognized as a chemoresistant tumor with dismal prognosis. In previous studies, we observed significant alterations in the serum sphingolipids of patients with HCC. This study aimed to investigate the in vitro effects of sorafenib, which is the most widely used systemic HCC medication, on the sphingolipid pathway as well as the effects of inhibiting the sphingolipid pathway in HCC. Huh7.5 and HepG2 cells were stimulated with sorafenib, and inhibitors of the sphingolipid pathway and cell proliferation, viability, and concentrations of bioactive metabolites were assessed. We observed a significant downregulation of cell proliferation and viability and a simultaneous upregulation of dihydroceramides upon sorafenib stimulation. Interestingly, fumonisin B1 (FB1) and the general sphingosine kinase inhibitor SKI II were able to inhibit cell proliferation more prominently in HepG2 and Huh7.5 cells, whereas there were no consistent effects on the formation of dihydroceramides, thus implying an involvement of distinct metabolic pathways. In conclusion, our study demonstrates a significant downregulation of HCC proliferation upon sorafenib, FB1, and SKI II treatment, whereas it seems they exert antiproliferative effects independently from sphingolipids. Certainly, further data would be required to elucidate the potential of FB1 and SKI II as putative novel therapeutic targets in HCC.
Author: | Katja Jakobi, Sandra Beyer, Alexander Koch, Dominique Jeanette ThomasORCiDGND, Stephanie SchwalmGND, Stefan ZeuzemORCiDGND, Josef PfeilschifterGND, Georgios Grammatikos |
---|---|
URN: | urn:nbn:de:hebis:30:3-544611 |
DOI: | https://doi.org/10.3390/ijms21072409 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/32244391 |
Parent Title (English): | International journal of molecular sciences |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2020/03/31 |
Date of first Publication: | 2020/03/31 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2020/04/09 |
Tag: | HCC; SKI II; dihydroceramide; fumonisin B1; liver |
Volume: | 21 |
Issue: | 2409 |
Page Number: | 21 |
Note: | This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited |
HeBIS-PPN: | 463907655 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 4.0 |