DC 欄位 | 值 | 語言 |
dc.contributor | 臺大醫院-內科部;臺大醫院新竹分院; | en |
dc.contributor.author | Ko, Jen-Chung | en |
dc.contributor.author | Chen, Huang-Jen | en |
dc.contributor.author | Huang, Yu-Ching | en |
dc.contributor.author | Tseng, Sheng-Chieh | en |
dc.contributor.author | Weng, Shao-Hsing | en |
dc.contributor.author | Wo, Ting-Yu | en |
dc.contributor.author | Huang, Yi-Jhen | en |
dc.contributor.author | Chiu, Hsien-Chun | en |
dc.contributor.author | Tsai, Min-Shao | en |
dc.contributor.author | Chiou, Robin Y. Y. | en |
dc.contributor.author | Lin, Yun-Wei | en |
dc.creator | Ko, Jen-Chung;Chen, Huang-Jen;Huang, Yu-Ching;Tseng, Sheng-Chieh;Weng, Shao-Hsing;Wo, Ting-Yu;Huang, Yi-Jhen;Chiu, Hsien-Chun;Tsai, Min-Shao;Chiou, Robin Y. Y.;Lin, Yun-Wei | en |
dc.date | 2012 | en |
dc.date.accessioned | 2014-02-14T07:05:26Z | - |
dc.date.accessioned | 2018-07-11T07:03:32Z | - |
dc.date.available | 2014-02-14T07:05:26Z | - |
dc.date.available | 2018-07-11T07:03:32Z | - |
dc.date.issued | 2012 | - |
dc.identifier.uri | http://ntur.lib.ntu.edu.tw//handle/246246/259359 | - |
dc.description.abstract | Heat shock protein 90 (HSP90) is an exciting new target in cancer therapy. Repair protein Rad51 is involved in protecting non-small cell lung cancer (NSCLC) cell lines against chemotherapeutic agent-induced cytotoxicity. This study investigated the role of Rad51 expression in HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)-induced cytotoxicity in two NSCLC cell lines, A549 and H1975. The 17-AAG treatment decreased cellular Rad51 protein and mRNA levels and phosphorylated MKK1/2-ERK1/2 protein levels, and disrupted the HSP90 and Rad51 interaction. This triggered Rad51 protein degradation through the 26S proteasome pathway. The 17-AAG treatment also decreased the NSCLC cells' DNA repair capacity, which was restored by the forced expression of the Flag-Rad51 vector. Specific inhibition of Rad51 expression by siRNA further enhanced 17-AAG-induced cytotoxicity. In contrast, enhanced ERK1/2 activation by the constitutively active MKK1/2 (MKK1/2-CA) vector significantly restored the 17-AAG-reduced Rad51 protein levels and cell viability. Arachidin-1, an antioxidant stilbenoid, further decreased Rad51 expression and augmented the cytotoxic effect and growth inhibition of 17-AAG. The 17-AAG and arachidin-1 -induced synergistic cytotoxic effects and decreased DNA repair capacity were abrogated in lung cancer cells with MKK1/2-CA or Flag-Rad51 expression vector transfection. In conclusion, HSP90 inhibition induces cytotoxicity by down-regulating Rad51 expression and DNA repair capacity in NSCLC cells. (C) 2012 Elsevier Inc. All rights reserved. | en |
dc.format.extent | 109 bytes | - |
dc.format.mimetype | text/html | - |
dc.language | en-us | en |
dc.relation | Regul. Toxicol. Pharmacol., 64(3), 415-424 | en |
dc.relation.ispartof | Regul. Toxicol. Pharmacol. | - |
dc.subject | HSP90 | en |
dc.subject | Rad51 | en |
dc.subject | Cytotoxicity | en |
dc.subject | DNA repair capacity | en |
dc.subject | Non-small cell lung cancer | en |
dc.subject | ERK1/2 | en |
dc.subject | Arachidin-1 | en |
dc.subject.classification | [SDGs]SDG3 | - |
dc.title | HSP90 inhibition induces cytotoxicity via down-regulation of Rad51 expression and DNA repair capacity in non-small cell lung cancer cells | en |
dc.relation.pages | 415-424 | - |
dc.relation.journalvolume | 64 | - |
dc.relation.journalissue | 3 | - |
dc.identifier.uri.fulltext | http://ntur.lib.ntu.edu.tw/bitstream/246246/259359/1/index.html | - |
item.grantfulltext | open | - |
item.fulltext | with fulltext | - |
顯示於: | 醫學系
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