Hexokinase-II Inhibition Synergistically Augments the Anti-tumor Efficacy of Sorafenib in Hepatocellular Carcinoma
DC Field | Value | Language |
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dc.contributor.author | Yoo, Jeong-Ju | - |
dc.contributor.author | Yu, Su Jong | - |
dc.contributor.author | Na, Juri | - |
dc.contributor.author | Kim, Kyungmin | - |
dc.contributor.author | Cho, Young Youn | - |
dc.contributor.author | Lee, Yun Bin | - |
dc.contributor.author | Cho, Eun Ju | - |
dc.contributor.author | Lee, Jeong-Hoon | - |
dc.contributor.author | Kim, Yoon Jun | - |
dc.contributor.author | Youn, Hyewon | - |
dc.contributor.author | Yoon, Jung-Hwan | - |
dc.date.accessioned | 2021-08-11T10:23:25Z | - |
dc.date.available | 2021-08-11T10:23:25Z | - |
dc.date.issued | 2019-03-21 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.issn | 1422-0067 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/4645 | - |
dc.description.abstract | This study aimed to examine whether inhibition of hexokinase (HK)-II activity enhances the efficacy of sorafenib in in-vivo models of hepatocellular carcinoma (HCC), and to evaluate the prognostic implication of HK-II expression in patients with HCC. We used 3-bromopyruvate (3-BP), a HK-II inhibitor to target HK-II. The human HCC cell line was tested as both subcutaneous and orthotopic tumor xenograft models in BALB/c nu/nu mice. The prognostic role of HK-II was evaluated in data from HCC patients in The Cancer Genome Atlas (TCGA) database and validated in patients treated with sorafenib. Quantitative real-time PCR, western blot analysis, and immunohistochemical staining revealed that HK-II expression is upregulated in the presence of sorafenib. Further analysis of the endoplasmic reticulum-stress network model in two different murine HCC models showed that the introduction of additional stress by 3-BP treatment synergistically increased the in vivo/vitro efficacy of sorafenib. We found that HCC patients with increased HK-II expression in the TCGA database showed poor overall survival, and also confirmed similar results for TCGA database HCC patients who had undergone sorafenib treatment. These results suggest that HK-II is a promising therapeutic target to enhance the efficacy of sorafenib and that HK-II expression might be a prognostic factor in HCC. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Multidisciplinary Digital Publishing Institute (MDPI) | - |
dc.title | Hexokinase-II Inhibition Synergistically Augments the Anti-tumor Efficacy of Sorafenib in Hepatocellular Carcinoma | - |
dc.type | Article | - |
dc.publisher.location | 스위스 | - |
dc.identifier.doi | 10.3390/ijms20061292 | - |
dc.identifier.scopusid | 2-s2.0-85062938020 | - |
dc.identifier.wosid | 000465523400019 | - |
dc.identifier.bibliographicCitation | International Journal of Molecular Sciences, v.20, no.6 | - |
dc.citation.title | International Journal of Molecular Sciences | - |
dc.citation.volume | 20 | - |
dc.citation.number | 6 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.subject.keywordPlus | ENERGY-METABOLISM | - |
dc.subject.keywordPlus | RESISTANCE | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | 3-BROMOPYRUVATE | - |
dc.subject.keywordPlus | PROLIFERATION | - |
dc.subject.keywordPlus | INDUCTION | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordPlus | ENHANCEMENT | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordAuthor | hepatocellular carcinoma | - |
dc.subject.keywordAuthor | sorafenib | - |
dc.subject.keywordAuthor | hexokinase inhibitor | - |
dc.subject.keywordAuthor | bromopyruvate | - |
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