Abstract

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.

Details

Title
Therapeutic effects of the PKR inhibitor C16 suppressing tumor proliferation and angiogenesis in hepatocellular carcinoma in vitro and in vivo
Author
Watanabe, Takao 1 ; Ninomiya Hiroko 2 ; Saitou Takashi 3 ; Sota, Takanezawa 2 ; Yamamoto, Shin 4 ; Imai Yusuke 1 ; Yoshida Osamu 1 ; Kawakami Ryosuke 2 ; Hirooka Masashi 1 ; Abe, Masanori 1 ; Imamura Takeshi 3 ; Hiasa Yoichi 1 

 Department of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Toon, Japan (GRID:grid.255464.4) (ISNI:0000 0001 1011 3808) 
 Department of Molecular Medicine for Pathogenesis, Graduate School of Medicine, Ehime University, Toon, Japan (GRID:grid.255464.4) (ISNI:0000 0001 1011 3808) 
 Department of Molecular Medicine for Pathogenesis, Graduate School of Medicine, Ehime University, Toon, Japan (GRID:grid.255464.4) (ISNI:0000 0001 1011 3808); Translational Research Center, Ehime University Hospital, Toon, Japan (GRID:grid.452478.8) (ISNI:0000 0004 0621 7227) 
 Department of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Toon, Japan (GRID:grid.255464.4) (ISNI:0000 0001 1011 3808); Department of Lifestyle-related Medicine and Endocrinology, Graduate School of Medicine, Ehime University, Toon, Japan (GRID:grid.255464.4) (ISNI:0000 0001 1011 3808) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2380032389
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.