DC Field | Value | Language |
---|---|---|
dc.contributor.author | Yang, Hannah | ko |
dc.contributor.author | Lee, Mi-Hee | ko |
dc.contributor.author | Park, Intae | ko |
dc.contributor.author | Jeon, Hanwool | ko |
dc.contributor.author | Choi, Junyoung | ko |
dc.contributor.author | Seo, Seyoung | ko |
dc.contributor.author | Kim, Sang-We | ko |
dc.contributor.author | Koh, Gou Young | ko |
dc.contributor.author | Park, Kang-Seo | ko |
dc.contributor.author | Lee, Dae Ho | ko |
dc.date.accessioned | 2018-01-22T02:04:05Z | - |
dc.date.available | 2018-01-22T02:04:05Z | - |
dc.date.created | 2017-12-18 | - |
dc.date.created | 2017-12-18 | - |
dc.date.issued | 2017-12 | - |
dc.identifier.citation | CANCER LETTERS, v.411, pp.19 - 26 | - |
dc.identifier.issn | 0304-3835 | - |
dc.identifier.uri | http://hdl.handle.net/10203/237152 | - |
dc.description.abstract | Small cell lung cancer (SCLC) cannot be efficiently controlled using existing chemotherapy and radiotherapy approaches, indicating the need for new therapeutic strategies. Although ABT-737, a B-cell lymphoma-2 (BCL-2) inhibitor, exerts anticancer effects against BCL-2-expressing SCLC, monotherapy with ABT-737 is associated with limited clinical activity because of the development of resistance and toxicity. Here, we examined whether combination therapy with ABT-737 and heat shock protein 90 (HSP90) inhibitor NVP-AUY922 exerted synergistic anticancer effects on SCLC. We found that the combination of ABT-737 and NVP-AUY922 synergistically induced the apoptosis of BCL-2-expressing SCLC cells. NVP-AUY922 downregulated the expression of AKT and ERK, which activate MCL-1 to induce resistance against ABT-737. The synergistic effect was also partly due to blocking NF-kappa B activation, which induces anti-apoptosis protein expressions. However, interestingly, targeting BCL-2 and MCL-1 or BCL2 and NF-kappa B did not induce the cytotoxicity. In conclusion, our study showed that combination of BCL2 inhibitor with HSP90 inhibitor increased activity in in vitro and in vivo study in only BCL-2 expressing SCLC compared to either single BCL2 inhibitor or HSP inhibitor. The enhanced activity might be led by blocking several apoptotic pathways simultaneously rather than a specific pathway. (c) 2017 Elsevier B.V. All rights reserved. | - |
dc.language | English | - |
dc.publisher | ELSEVIER IRELAND LTD | - |
dc.subject | INDUCED APOPTOSIS | - |
dc.subject | PHOSPHORYLATION | - |
dc.subject | MCL-1 | - |
dc.subject | RESISTANCE | - |
dc.subject | LEUKEMIA | - |
dc.subject | FAMILY | - |
dc.subject | ONCOGENESIS | - |
dc.subject | ACTIVATION | - |
dc.subject | THERAPIES | - |
dc.subject | HALLMARKS | - |
dc.title | HSP90 inhibitor (NVP-AUY922) enhances the anti-cancer effect of BCL-2 inhibitor (ABT-737) in small cell lung cancer expressing BCL-2 | - |
dc.type | Article | - |
dc.identifier.wosid | 000416299700003 | - |
dc.identifier.scopusid | 2-s2.0-85030871645 | - |
dc.type.rims | ART | - |
dc.citation.volume | 411 | - |
dc.citation.beginningpage | 19 | - |
dc.citation.endingpage | 26 | - |
dc.citation.publicationname | CANCER LETTERS | - |
dc.identifier.doi | 10.1016/j.canlet.2017.09.040 | - |
dc.contributor.localauthor | Koh, Gou Young | - |
dc.contributor.nonIdAuthor | Yang, Hannah | - |
dc.contributor.nonIdAuthor | Lee, Mi-Hee | - |
dc.contributor.nonIdAuthor | Jeon, Hanwool | - |
dc.contributor.nonIdAuthor | Choi, Junyoung | - |
dc.contributor.nonIdAuthor | Seo, Seyoung | - |
dc.contributor.nonIdAuthor | Kim, Sang-We | - |
dc.contributor.nonIdAuthor | Park, Kang-Seo | - |
dc.contributor.nonIdAuthor | Lee, Dae Ho | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Small cell lung cancer | - |
dc.subject.keywordAuthor | BCL-2 inhibitor | - |
dc.subject.keywordAuthor | HSP90 inhibitor | - |
dc.subject.keywordAuthor | Combination therapy | - |
dc.subject.keywordPlus | INDUCED APOPTOSIS | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordPlus | MCL-1 | - |
dc.subject.keywordPlus | RESISTANCE | - |
dc.subject.keywordPlus | LEUKEMIA | - |
dc.subject.keywordPlus | FAMILY | - |
dc.subject.keywordPlus | ONCOGENESIS | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | THERAPIES | - |
dc.subject.keywordPlus | HALLMARKS | - |
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