Therapeutic effects of the PKR inhibitor C16 suppressing tumor proliferation and angiogenesis in hepatocellular carcinoma in vitro and in vivo

Autor: Hiroko Ninomiya, Yoichi Hiasa, Ryosuke Kawakami, Sota Takanezawa, Masanori Abe, Takao Watanabe, Takeshi Imamura, Shin Yamamoto, Masashi Hirooka, Takashi Saitou, Yusuke Imai, Osamu Yoshida
Rok vydání: 2020
Předmět:
Vascular Endothelial Growth Factor A
0301 basic medicine
Vascular Endothelial Growth Factor B
Indoles
Hepatocellular carcinoma
Angiogenesis
lcsh:Medicine
Mice
eIF-2 Kinase
0302 clinical medicine
Epidermal growth factor
lcsh:Science
Platelet-Derived Growth Factor
Mice
Inbred BALB C
Multidisciplinary
Neovascularization
Pathologic
Molecular medicine
Hepatocyte Growth Factor
Chemistry
Liver Neoplasms
food and beverages
Hep G2 Cells
Proto-Oncogene Proteins c-sis
030220 oncology & carcinogenesis
Female
lipids (amino acids
peptides
and proteins)
Hepatocyte growth factor
medicine.drug
Carcinoma
Hepatocellular
Cell Survival
Mice
Nude
Antineoplastic Agents
Article
03 medical and health sciences
In vivo
Cell Line
Tumor
medicine
Animals
Humans
MTT assay
RNA
Messenger
Viability assay
Cell Proliferation
Epidermal Growth Factor
lcsh:R
Xenograft Model Antitumor Assays
digestive system diseases
Fibroblast Growth Factors
Thiazoles
030104 developmental biology
Tumor progression
Cell culture
Cancer research
lcsh:Q
Zdroj: Scientific Reports
Scientific Reports, Vol 10, Iss 1, Pp 1-9 (2020)
ISSN: 2045-2322
DOI: 10.1038/s41598-020-61579-x
Popis: 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.
Databáze: OpenAIRE
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