Selumetinib Inhibits Melanoma Metastasis to Mouse Liver via Suppression of EMT-targeted Genes
DC Field | Value | Language |
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dc.contributor.author | Ryu, Seung-Hee | - |
dc.contributor.author | Heo, Seung-Ho | - |
dc.contributor.author | Park, Eun Young | - |
dc.contributor.author | Choi, Kyung-Chul | - |
dc.contributor.author | Ryu, Je-Won | - |
dc.contributor.author | Lee, Seok Ho | - |
dc.contributor.author | Lee, Sang-Wook | - |
dc.date.available | 2020-02-27T19:44:28Z | - |
dc.date.created | 2020-02-07 | - |
dc.date.issued | 2017-02 | - |
dc.identifier.issn | 0250-7005 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/6472 | - |
dc.description.abstract | Aim: We investigated the therapeutic effects of a mitogen-activated protein (MEK) inhibitor, selumetinib, in a hepatic melanoma metastasis model and studied its possible mechanism of action. Materials and Methods: Melanoma cell lines were exposed to selumetinib under different experimental conditions. We established a mouse model of liver metastasis and treated mice orally with vehicle or selumetinib and then evaluated metastasis progress. Results: Growth inhibition was observed in melanoma cells as a consequence of G(1)-phase cell-cycle arrest and the subsequent induction of apoptosis in a doseand time-dependent manner. Mice with established liver metastases that were treated with selumetinib exhibited significantly less tumor progression than vehicle-treated mice. c-Myc expression in metastasized liver tissues were suppressed by selumetinib. Moreover, oral treatment with selumetinib modulated expression of epithelial-tomesenchymal transition-and metastasis-related genes, including integrin alpha-5 (ITGA5), jagged 1 (JAG1), zinc finger E-box-binding homeobox 1 (ZEB1), NOTCH, and serpin peptidase inhibitor clade E (SERPINE1). Conclusion: We established a mouse model of hepatic metastasis using a human melanoma cell line, such models are essential in elucidating the therapeutic effects of anti-metastatic drugs. Our data suggest the possibility that selumetinib presents a new strategy to treat liver metastasis in patients with melanoma by suppressing epithelial-to-mesenchymal transition-related genes. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | INT INST ANTICANCER RESEARCH | - |
dc.relation.isPartOf | ANTICANCER RESEARCH | - |
dc.subject | AZD6244 ARRY-142886 | - |
dc.subject | KINASE INHIBITOR | - |
dc.subject | PHASE-I | - |
dc.subject | EXPRESSION | - |
dc.subject | CELLS | - |
dc.subject | TRIAL | - |
dc.subject | RAF | - |
dc.subject | ACTIVATION | - |
dc.subject | SURVIVAL | - |
dc.subject | PATHWAY | - |
dc.title | Selumetinib Inhibits Melanoma Metastasis to Mouse Liver via Suppression of EMT-targeted Genes | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000396901200025 | - |
dc.identifier.doi | 10.21873/anticanres.11354 | - |
dc.identifier.bibliographicCitation | ANTICANCER RESEARCH, v.37, no.2, pp.607 - 614 | - |
dc.identifier.scopusid | 2-s2.0-85013675625 | - |
dc.citation.endPage | 614 | - |
dc.citation.startPage | 607 | - |
dc.citation.title | ANTICANCER RESEARCH | - |
dc.citation.volume | 37 | - |
dc.citation.number | 2 | - |
dc.contributor.affiliatedAuthor | Lee, Seok Ho | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | MEK inhibitor | - |
dc.subject.keywordAuthor | selumetinib (AZD6244) | - |
dc.subject.keywordAuthor | liver metastasis | - |
dc.subject.keywordAuthor | melanoma | - |
dc.subject.keywordAuthor | EMT | - |
dc.subject.keywordPlus | AZD6244 ARRY-142886 | - |
dc.subject.keywordPlus | KINASE INHIBITOR | - |
dc.subject.keywordPlus | PHASE-I | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | TRIAL | - |
dc.subject.keywordPlus | RAF | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | SURVIVAL | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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