Cited 15 times in
AZD6244 inhibits cisplatin-induced ERK1/2 activation and potentiates cisplatin-associated cytotoxicity in K-ras G12D preclinical models
DC Field | Value | Language |
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dc.contributor.author | 장윤수 | - |
dc.contributor.author | 김세규 | - |
dc.contributor.author | 김아름 | - |
dc.contributor.author | 김은영 | - |
dc.date.accessioned | 2016-02-04T10:56:15Z | - |
dc.date.available | 2016-02-04T10:56:15Z | - |
dc.date.issued | 2015 | - |
dc.identifier.issn | 0304-3835 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/139308 | - |
dc.description.abstract | Although cisplatin has been widely used as a component of standard treatments for advanced non-small cell lung cancers (NSCLC) with KRAS-activating mutations, clinical outcomes remain suboptimal. Among the resistance mechanisms to cisplatin, activation of the MAPK cascade, which plays an important role in cancer cell stress and death, offers a promising therapeutic target. Using KRAS-mutant NSCLC cells and a mouse model, we evaluated the efficacy of adding the MEK1/2 inhibitor AZD6244 as an addition for cisplatin-based chemotherapy. Cisplatin increased phosphorylation of MEK1/2 and ERK1/2 and reduced Bcl-2 like 11 (BIM) expression in NSCLC cells and the mouse model. BIM silencing in NSCLC cells using shRNA led to a blunted cytotoxic response to cisplatin, while prevention of BIM loss with the MEK1/2 inhibitor synergized cisplatin-mediated cell death. The combination of cisplatin and AZD6244 yielded a superior response to cisplatin alone in K-ras mice. In conclusion, an MEK1/2 inhibitor potentiated the anti-tumor effects of cisplatin in KRAS-dependent lung cancer cells and an animal model through inhibition of BIM degradation. These findings warrant further studies of clinical applications of MEK1/2 inhibitors in cisplatin-based chemotherapy for lung cancer. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 85~91 | - |
dc.relation.isPartOf | CANCER LETTERS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Apoptosis/drug effects | - |
dc.subject.MESH | Apoptosis Regulatory Proteins/metabolism | - |
dc.subject.MESH | Bcl-2-Like Protein 11 | - |
dc.subject.MESH | Benzimidazoles/administration & dosage* | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung/drug therapy* | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung/genetics | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung/pathology | - |
dc.subject.MESH | Cisplatin/administration & dosage | - |
dc.subject.MESH | Drug Resistance, Neoplasm/drug effects | - |
dc.subject.MESH | Drug Synergism | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | MAP Kinase Kinase 1/biosynthesis | - |
dc.subject.MESH | MAP Kinase Kinase 1/genetics* | - |
dc.subject.MESH | MAP Kinase Signaling System/genetics* | - |
dc.subject.MESH | Membrane Proteins/metabolism | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Proto-Oncogene Proteins/genetics* | - |
dc.subject.MESH | Proto-Oncogene Proteins/metabolism | - |
dc.subject.MESH | Proto-Oncogene Proteins p21(ras) | - |
dc.subject.MESH | ras Proteins/genetics* | - |
dc.title | AZD6244 inhibits cisplatin-induced ERK1/2 activation and potentiates cisplatin-associated cytotoxicity in K-ras G12D preclinical models | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Yonsei Biomedical Research Center (연세의생명연구원) | - |
dc.contributor.googleauthor | Eun Young Kim | - |
dc.contributor.googleauthor | Arum Kim | - |
dc.contributor.googleauthor | Se Kyu Kim | - |
dc.contributor.googleauthor | Yoon Soo Chang | - |
dc.identifier.doi | 10.1016/j.canlet.2014.12.041 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A03456 | - |
dc.contributor.localId | A00602 | - |
dc.contributor.localId | A00680 | - |
dc.contributor.localId | A00811 | - |
dc.relation.journalcode | J00448 | - |
dc.identifier.eissn | 1872-7980 | - |
dc.identifier.pmid | 25541062 | - |
dc.identifier.url | http://www.sciencedirect.com/science/article/pii/S030438351400799X | - |
dc.subject.keyword | Bcl2-like 11 (BIM) | - |
dc.subject.keyword | Cisplatin | - |
dc.subject.keyword | KRAS | - |
dc.subject.keyword | MEK1/2 inhibitor | - |
dc.subject.keyword | NSCLC | - |
dc.contributor.alternativeName | Chang, Yoon Soo | - |
dc.contributor.alternativeName | Kim, Se Kyu | - |
dc.contributor.alternativeName | Kim, A Rum | - |
dc.contributor.alternativeName | Kim, Eun Young | - |
dc.contributor.affiliatedAuthor | Chang, Yoon Soo | - |
dc.contributor.affiliatedAuthor | Kim, Se Kyu | - |
dc.contributor.affiliatedAuthor | Kim, A Rum | - |
dc.contributor.affiliatedAuthor | Kim, Eun Young | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 358 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 85 | - |
dc.citation.endPage | 91 | - |
dc.identifier.bibliographicCitation | CANCER LETTERS, Vol.358(1) : 85-91, 2015 | - |
dc.identifier.rimsid | 45558 | - |
dc.type.rims | ART | - |
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