TY  - JOUR
A1  - Jakobi, Katja
A1  - Beyer, Sandra
A1  - Koch, Alexander
A1  - Thomas, Dominique Jeanette
A1  - Schwalm, Stephanie
A1  - Zeuzem, Stefan
A1  - Pfeilschifter, Josef
A1  - Grammatikos, Georgios
T1  - Sorafenib treatment and modulation of the sphingolipid pathway affect proliferation and viability of hepatocellular carcinoma In vitro
T2  - International journal of molecular sciences
N2  - 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.
KW  - liver
KW  - HCC
KW  - dihydroceramide
KW  - SKI II
KW  - fumonisin B1
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/54461
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-544611
N1  - 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
VL  - 21
IS  - 2409
PB  - MDPI
CY  - Basel
ER  -