Therapeutic effects of the PKR inhibitor C16 suppressing tumor proliferation and angiogenesis in hepatocellular carcinoma in vitro and in vivo.
Animals
Antineoplastic Agents
/ pharmacology
Carcinoma, Hepatocellular
/ drug therapy
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Epidermal Growth Factor
/ genetics
Female
Fibroblast Growth Factors
/ genetics
Hep G2 Cells
Hepatocyte Growth Factor
/ genetics
Humans
Indoles
/ pharmacology
Liver Neoplasms
/ drug therapy
Mice
Mice, Inbred BALB C
Mice, Nude
Neovascularization, Pathologic
/ drug therapy
Platelet-Derived Growth Factor
/ genetics
Proto-Oncogene Proteins c-sis
/ genetics
RNA, Messenger
/ genetics
Thiazoles
/ pharmacology
Vascular Endothelial Growth Factor A
/ genetics
Vascular Endothelial Growth Factor B
/ genetics
Xenograft Model Antitumor Assays
eIF-2 Kinase
/ antagonists & inhibitors
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
20 03 2020
20 03 2020
Historique:
received:
02
09
2019
accepted:
21
01
2020
entrez:
22
3
2020
pubmed:
22
3
2020
medline:
26
11
2020
Statut:
epublish
Résumé
The therapeutic effects of C16, which is an inhibitor of RNA-dependent protein kinase (PKR), on growth of hepatocellular carcinoma (HCC) cells and tumor progression in vitro and in vivo were evaluated. Huh7 cells, a human HCC cell line, were used. The effects of C16 on cell viability were evaluated with the MTT assay, and real-time RT-PCR was performed. Huh7 cells were grafted into immunodeficient mice, and the in vivo effects of C16 on tumorigenesis were examined. C16 suppressed proliferation of HCC cells in a dose-dependent manner in vitro. Mouse models with xenograft transplantation showed that the inhibitor suppressed the growth of HCC cells in vivo. Moreover, C16 decreased angiogenesis in HCC tissue in the xenograft model. Consistent with these results in mice, transcript levels of vascular endothelial growth factor-A and factor-B, platelet-derived growth factor-A and factor-B, fibroblast growth factor-2, epidermal growth factor, and hepatocyte growth factor, which are angiogenesis-related growth factors, were significantly decreased by C16 in vitro. In conclusion, the PKR inhibitor C16 blocked tumor cell growth and angiogenesis via a decrease in mRNA levels of several growth factors. C16 may be useful in the treatment of HCC.
Identifiants
pubmed: 32198380
doi: 10.1038/s41598-020-61579-x
pii: 10.1038/s41598-020-61579-x
pmc: PMC7083831
doi:
Substances chimiques
Antineoplastic Agents
0
Fgf20 protein, mouse
0
GW 506033X
0
Indoles
0
Platelet-Derived Growth Factor
0
Proto-Oncogene Proteins c-sis
0
RNA, Messenger
0
Thiazoles
0
Vascular Endothelial Growth Factor A
0
Vascular Endothelial Growth Factor B
0
platelet-derived growth factor A
0
vascular endothelial growth factor A, mouse
0
vascular endothelial growth factor B, mouse
0
Fibroblast Growth Factors
62031-54-3
Epidermal Growth Factor
62229-50-9
Hepatocyte Growth Factor
67256-21-7
eIF-2 Kinase
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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