The inhibitor of protein kinase R (PKR) suppresses tumor proliferation and angiogenesis in hepatocellular carcinoma in vitro and in vivo models
| Project/Area Number |
18K15818
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Ehime University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 肝細胞癌 / PKR / 細胞増殖 / 血管新生 / 阻害剤 / 増殖因子 / 代謝 / HCV / メチル化 / NASH |
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| Outline of Final Research Achievements |
We tested the effect of protein kinase R (PKR) inhibitor C16 on proliferation of HCC Huh7 cells in vitro and tumor progression and angiogenesis of tumor bearing mouse of Huh7 in vivo.
C16 suppressed proliferation of Huh7 cells in a dose-dependent manner in vitro evaluated with the MTT assay. 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.
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| Academic Significance and Societal Importance of the Research Achievements |
現在、肝細胞癌に対する治療は、手術、内科的な局所治療としてRFA、TACEなどが用いられている。しかし肝細胞癌患者の高齢化、その高い再発率から患者への負担の少ない薬物治療の開発が必要である。治療効果のエビデンスのある薬物もごく限られているのが現状である。本研究では細胞株とマウスを用いた検討を行い、PKR阻害剤により肝細胞癌の増殖、血管新生が抑制されることを示した。PKRをターゲットとした治療は肝細胞癌における新規治療となり得ると考えられた。
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Report
(3 results)
Research Products
(12 results)
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[Journal Article] Therapeutic Effects of the PKR Inhibitor C16 Suppressing Tumor Proliferation and Angiogenesis in Hepatocellular Carcinoma in Vitro and in Vivo.2020
Author(s)
Watanabe T, Ninomiya H, Saitou T, Takanezawa S, Yamamoto S, Imai Y, Yoshida O, Kawakami R, Hirooka M, Abe M, Imamura T, Hiasa Y.
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Journal Title
Scientific Reports
Volume: 20;10(1)
Issue: 1
Pages: 5133-5133
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Advanced fibrosis of non-alcoholic steatohepatitis affects the significance of lipoprotein(a) as a cardiovascular risk factor2020
Author(s)
Konishi K, Miyake T, Furukawa S, Senba H, Kanzaki S, Nakaguchi H, Yukimoto A, Nakamura Y, Watanabe T, Koizumi Y, Yoshida O, Tokumoto Y, Hirooka M, Kumagi T, Abe M, Matsuura B, Hiasa Y.
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Journal Title
Atherosclerosis
Volume: 299
Pages: 32-37
DOI
Related Report
Peer Reviewed
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[Journal Article] Predictors of hepatocellular carcinoma occurrence after direct-acting antiviral therapy in patients with hepatitis C virus infection.2019
Author(s)
Watanabe T, Tokumoto Y, Joko K, Michitaka K, Horiike N, Tanaka Y, Tada F, Kisaka Y, Nakanishi S, Yamauchi K, Yukimoto A, Hirooka M, Abe M, Hiasa Y.
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Journal Title
Hepatology Research
Volume: Feb;49(2)
Issue: 2
Pages: 136-146
DOI
Related Report
Peer Reviewed
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[Journal Article] Using ALBI score at the start of sorafenib treatment to predict regorafenib treatment candidates in patients with hepatocellular carcinoma.2019
Author(s)
Yukimoto A, Hirooka M, Hiraoka A, Michitaka K, Ochi H, Joko K, Imai Y, Watanabe T, Koizumi Y, Yoshida O, Abe M, Hiasa Y.
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Journal Title
Japanese Journal of Clinical Oncology
Volume: Jan 1;49(1)
Issue: 1
Pages: 42-47
DOI
Related Report
Peer Reviewed
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