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Down-Regulation of TGF-β Expression Sensitizes the Resistance of Hepatocellular Carcinoma Cells to Sorafenib.

DC FieldValueLanguage
dc.contributor.author송재진-
dc.contributor.author최혜진-
dc.date.accessioned2018-07-20T07:51:29Z-
dc.date.available2018-07-20T07:51:29Z-
dc.date.issued2017-
dc.identifier.issn0513-5796-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/160599-
dc.description.abstractPURPOSE: Sorafenib, a multikinase inhibitor, is the standard therapy for patients with advanced-stage hepatocellular carcinoma (HCC). However, resistance develops to the treatment, therefore, we tried to unravel the underlying mechanism in the resistance of HCC cells to sorafenib via the development of more effective therapeutic strategies. MATERIALS AND METHODS: Various liver cancer cell lines were treated with either sorafenib only or with sorafenib after infection of adenovirus expressing short hairpin RNA (shRNA) against transforming growth factor-β (TGF-β) and p38 activity was examined using western blotting. RESULTS: p38 MAP kinase activity was inhibited by low concentrations of sorafenib, which could potentially lead to sorafenib resistance in HCC cell lines. Subsequently, we used constitutive form of MKK3/6 (MKK3/6E) to confirm that massive cell death was induced by the activation of p38, and demonstrated the ability to activate p38 without any stimulation. In addition, sorafenib resistance was reduced by the activation of p38. Subsequently, we confirmed that TGF-β shRNA effectively recovered the phosphorylation of p38 inhibited by sorafenib, and increased the sensitivity of HCC cells to sorafenib, thereby inducing cell death and overcoming the resistance of HCC cells to sorafenib. CONCLUSION: Our study provides a new therapeutic strategy for HCC that overcomes the resistance of HCC to sorafenib by down-regulation of TGF-β.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherYonsei University-
dc.relation.isPartOfYONSEI MEDICAL JOURNAL-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAdenoviridae/metabolism-
dc.subject.MESHAnimals-
dc.subject.MESHAntineoplastic Agents/pharmacology-
dc.subject.MESHAntineoplastic Agents/therapeutic use-
dc.subject.MESHCarcinoma, Hepatocellular/metabolism*-
dc.subject.MESHCarcinoma, Hepatocellular/pathology*-
dc.subject.MESHCell Death/drug effects-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHDown-Regulation/drug effects*-
dc.subject.MESHDrug Resistance, Neoplasm/drug effects*-
dc.subject.MESHHumans-
dc.subject.MESHLiver Neoplasms/metabolism-
dc.subject.MESHLiver Neoplasms/pathology*-
dc.subject.MESHMice, Inbred BALB C-
dc.subject.MESHMice, Nude-
dc.subject.MESHNiacinamide/analogs & derivatives*-
dc.subject.MESHNiacinamide/pharmacology-
dc.subject.MESHNiacinamide/therapeutic use-
dc.subject.MESHPhenylurea Compounds/pharmacology*-
dc.subject.MESHPhenylurea Compounds/therapeutic use-
dc.subject.MESHPhosphorylation/drug effects-
dc.subject.MESHRNA, Small Interfering/metabolism-
dc.subject.MESHSignal Transduction/drug effects-
dc.subject.MESHTransforming Growth Factor beta/metabolism*-
dc.subject.MESHXenograft Model Antitumor Assays-
dc.subject.MESHp38 Mitogen-Activated Protein Kinases/metabolism-
dc.titleDown-Regulation of TGF-β Expression Sensitizes the Resistance of Hepatocellular Carcinoma Cells to Sorafenib.-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Life Science-
dc.contributor.googleauthorDongxu Kang-
dc.contributor.googleauthorZhezhu Han-
dc.contributor.googleauthorGeun-Hyeok Oh-
dc.contributor.googleauthorYeonsoo Joo-
dc.contributor.googleauthorHye Jin Choi-
dc.contributor.googleauthorJae J. Song-
dc.identifier.doi10.3349/ymj.2017.58.5.899-
dc.contributor.localIdA02056-
dc.contributor.localIdA04219-
dc.relation.journalcodeJ02813-
dc.identifier.eissn1976-2437-
dc.identifier.pmid28792132-
dc.subject.keywordHCC-
dc.subject.keywordTGF-β-
dc.subject.keywordadenovirus-
dc.subject.keywordp38-
dc.subject.keywordresistance-
dc.subject.keywordsorafenib-
dc.contributor.alternativeNameSong, Jae Jin-
dc.contributor.alternativeNameChoi, Hye Jin-
dc.contributor.affiliatedAuthorSong, Jae Jin-
dc.contributor.affiliatedAuthorChoi, Hye Jin-
dc.citation.volume58-
dc.citation.number5-
dc.citation.startPage899-
dc.citation.endPage909-
dc.identifier.bibliographicCitationYONSEI MEDICAL JOURNAL, Vol.58(5) : 899-909, 2017-
dc.identifier.rimsid40009-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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