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A novel HDAC inhibitor, CG200745, inhibits pancreatic cancer cell growth and overcomes gemcitabine resistance

DC FieldValueLanguage
dc.contributor.author송시영-
dc.contributor.author이희승-
dc.contributor.author김선아-
dc.date.accessioned2017-11-02T08:18:48Z-
dc.date.available2017-11-02T08:18:48Z-
dc.date.issued2017-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/154322-
dc.description.abstractPancreatic cancer is predominantly lethal, and is primarily treated using gemcitabine, with increasing resistance. Therefore, novel agents that increase tumor sensitivity to gemcitabine are needed. Histone deacetylase (HDAC) inhibitors are emerging therapeutic agents, since HDAC plays an important role in cancer initiation and progression. We evaluated the antitumor effect of a novel HDAC inhibitor, CG200745, combined with gemcitabine/erlotinib on pancreatic cancer cells and gemcitabine-resistant pancreatic cancer cells. Three pancreatic cancer-cell lines were used to evaluate the antitumor effect of CG200745 combined with gemcitabine/erlotinib. CG200745 induced the expression of apoptotic proteins (PARP and caspase-3) and increased the levels of acetylated histone H3. CG200745 with gemcitabine/erlotinib showed significant growth inhibition and synergistic antitumor effects in vitro. In vivo, gemcitabine/erlotinib and CG200745 reduced tumor size up to 50%. CG200745 enhanced the sensitivity of gemcitabine-resistant pancreatic cancer cells to gemcitabine, and decreased the level of ATP-binding cassette-transporter genes, especially multidrug resistance protein 3 (MRP3) and MRP4. The novel HDAC inhibitor, CG200745, with gemcitabine/erlotinib had a synergistic anti-tumor effect on pancreatic cancer cells. CG200745 significantly improved pancreatic cancer sensitivity to gemcitabine, with a prominent antitumor effect on gemcitabine-resistant pancreatic cancer cells. Therefore, improved clinical outcome is expected in the future.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherNature Publishing Group-
dc.relation.isPartOfSCIENTIFIC REPORTS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleA novel HDAC inhibitor, CG200745, inhibits pancreatic cancer cell growth and overcomes gemcitabine resistance-
dc.typeArticle-
dc.publisher.locationEngland-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Internal Medicine-
dc.contributor.googleauthorHee Seung Lee-
dc.contributor.googleauthorSoo Been Park-
dc.contributor.googleauthorSun A Kim-
dc.contributor.googleauthorSool Ki Kwon-
dc.contributor.googleauthorHyunju Cha-
dc.contributor.googleauthorDo Young Lee-
dc.contributor.googleauthorSeonggu Ro-
dc.contributor.googleauthorJoong Myung Cho-
dc.contributor.googleauthorSi Young Song-
dc.identifier.doi10.1038/srep41615-
dc.contributor.localIdA03349-
dc.contributor.localIdA02035-
dc.relation.journalcodeJ02646-
dc.identifier.eissn2045-2322-
dc.identifier.pmid28134290-
dc.contributor.alternativeNameSong, Si Young-
dc.contributor.alternativeNameLee, Hee Seung-
dc.contributor.affiliatedAuthorLee, Hee Seung-
dc.contributor.affiliatedAuthorSong, Si Young-
dc.citation.titleScientific Reports-
dc.citation.volume7-
dc.citation.startPage41615-
dc.identifier.bibliographicCitationSCIENTIFIC REPORTS, Vol.7 : 41615, 2017-
dc.date.modified2017-11-01-
dc.identifier.rimsid42891-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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