A Newly Established Murine Cell Line as a Model for Hepatocellular Cancer in Non-Alcoholic Steatohepatitis.
Animals
Antigens, Differentiation
/ metabolism
Biomarkers, Tumor
/ metabolism
Carcinoma, Hepatocellular
Cell Line, Tumor
Everolimus
/ pharmacology
Liver Neoplasms, Experimental
/ drug therapy
Mice
Morpholines
/ pharmacokinetics
Neoplastic Stem Cells
/ metabolism
Non-alcoholic Fatty Liver Disease
/ drug therapy
Pyrimidines
/ pharmacokinetics
Everolimus
KU-0063794
cell line
hepatocellular carcinoma
mTOR
non-alcoholic steatohepatitis
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
12 Nov 2019
12 Nov 2019
Historique:
received:
22
10
2019
revised:
07
11
2019
accepted:
08
11
2019
entrez:
16
11
2019
pubmed:
16
11
2019
medline:
2
4
2020
Statut:
epublish
Résumé
Non-alcoholic steatohepatitis (NASH) has become a major risk factor for hepatocellular cancer (HCC) due to the worldwide increasing prevalence of obesity. However, the pathophysiology of NASH and its progression to HCC is incompletely understood. Thus, the aim of this study was to generate a model specific NASH-derived HCC cell line. A murine NASH-HCC model was conducted and the obtained cancer cells (N-HCC25) were investigated towards chromosomal aberrations, the expression of cell type-specific markers, dependency on nutrients, and functional importance of mTOR. N-HCC25 exhibited several chromosomal aberrations as compared to healthy hepatocytes. Hepatocytic (HNF4), EMT (Twist, Snail), and cancer stem cell markers (CD44, EpCAM, CK19, Sox9) were simultaneously expressed in these cells. Proliferation highly depended on the supply of glucose and FBS, but not glutamine. Treatment with a second generation mTOR inhibitor (KU-0063794) resulted in a strong decrease of cell growth in a dose-dependent manner. In contrast, a first generation mTOR inhibitor (Everolimus) only slightly reduced cell proliferation. Cell cycle analyses revealed that the observed growth reduction was most likely due to G
Identifiants
pubmed: 31726709
pii: ijms20225658
doi: 10.3390/ijms20225658
pmc: PMC6888677
pii:
doi:
Substances chimiques
Antigens, Differentiation
0
Biomarkers, Tumor
0
Morpholines
0
Pyrimidines
0
Ku 0063794
81HJG228AB
Everolimus
9HW64Q8G6G
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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