The study to clarify the tumor suppressive effect of PKR inhibitor in hepatocellular carcinoma using in vivo imaging
| Project/Area Number |
16K19349
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Ehime University |
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Principal Investigator |
Watanabe Takao 愛媛大学, 医学部附属病院, 講師 (90650458)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | PKR / hepatocellular carcinoma / DNA methylation / PKR inhibitor / proliferation / HCV / 肝細胞癌 / メチル化 / C型肝炎ウイルス / 治療標的 / イメージング |
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| Outline of Final Research Achievements |
Double-stranded RNA-activated protein kinase R (PKR) is upregulated by hepatitis C virus (HCV), and also overexpressed in hepatocellular carcinoma (HCC) with HCV infection. In HCC cell line Huh 7, we elucidated PKR inhibitor administration significantly decrease tumor cell proliferation in a dose dependent manner by in vitro proliferation assay. To evaluate the tumor suppressive effect of PKR inhibitor in vivo, we inoculated Huh 7 cells subcutaneously into BALB/c-nu/nu mice. The mice were then injected i.p. every day with or without PKR inhibitor. Then PKR inhibitor suppressed the proliferation of HCC cells in a dose dependent manner. Moreover we identified DNA methylation level of several cancer related genes were changed by PKR-knockdown in HCV infected HCC cells using the human Methylation450 BeadChipTM. PKR promotes the proliferation of HCC cells, and PKR inhibitor could serve as an attractive therapeutic approach.
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Report
(3 results)
Research Products
(9 results)
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[Journal Article] Predictors of treatment efficacy and ALT non-normalization with sofosbuvir/ribavirin therapy for patients with hepatitis C virus genotype 2.2017
Author(s)
Watanabe T, Tokumoto Y, Joko K, Michitaka K, Horiike N, Tanaka Y, Tada F, Kisaka Y, Nakanishi S, Nonaka T, Yamauchi K, Hirooka M, Abe M, Hiasa Y.
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Journal Title
J Med Virol.
Volume: 89
Issue: 9
Pages: 1567-1573
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Downregulation of ANP32B exerts anti-apoptotic effects in hepatocellular carcinoma.2017
Author(s)
Ohno Y, Koizumi M, Nakayama H, Watanabe T, Hirooka M, Tokumoto Y, Kuroda T, Abe M, Fukuda S, Higashiyama S, Kumagi T, Hiasa Y.
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Journal Title
PLoS One.
Volume: 12
Issue: 5
Pages: 0177343-0177343
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] The epigenetic roles of protein kinase R in hepatocellular carcinoma with hepatitis C virus Infection, and possibility of PKR inhibitor as a therapeutic target2017
Author(s)
Takao Watanabe, Yoshio Tokumoto, Masashi Hirooka, Osamu Yoshida, Yohei Koizumi, Yusuke Imai, Yoshiko Nakamura, Masanori Abe1, Hiroko Ninomiya, Takeshi Imamura, Yoichi Hiasa
Organizer
The asian pacific association for the study of the liver single topic conference in Nagasaki
Related Report
Int'l Joint Research
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