https://scholars.lib.ntu.edu.tw/handle/123456789/568475
DC 欄位 | 值 | 語言 |
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dc.contributor.author | Chen K.-F. | en_US |
dc.contributor.author | Chen H.-L. | en_US |
dc.contributor.author | Shiau C.-W. | en_US |
dc.contributor.author | Liu C.-Y. | en_US |
dc.contributor.author | Chu P.-Y. | en_US |
dc.contributor.author | Tai W.-T. | en_US |
dc.contributor.author | Ichikawa K. | en_US |
dc.contributor.author | PEI-JER CHEN | en_US |
dc.contributor.author | ANN-LII CHENG | en_US |
dc.date.accessioned | 2021-07-03T03:34:22Z | - |
dc.date.available | 2021-07-03T03:34:22Z | - |
dc.date.issued | 2013 | - |
dc.identifier.issn | 0007-1188 | - |
dc.identifier.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84984558781&doi=10.1111%2fj.1476-5381.2012.02212.x&partnerID=40&md5=ff866b4ef1ae171654301e4fda5e7c4e | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/568475 | - |
dc.description.abstract | Background and Purpose: Previously, we have shown that sorafenib sensitizes hepatocellular carcinoma (HCC) to apoptosis induced by TNF-related apoptosis-inducing ligand (TNFSF10; TRAIL). Here, we report that sorafenib and SC-49 sensitize HCC cells to CS-1008, a novel anti-human death receptor 5 (TNFRSF10B) antibody. Experimental Approach: HCC cell lines (PLC5, Huh-7, and Hep3B) were treated with CS-1008 and/or sorafenib and analysed in terms of apoptosis and signal transductions. Key Results: SC-49 is a sorafenib derivative, which is devoid of kinase inhibitory activity. Both sorafenib and SC-49 down-regulated the phosphorylation of STAT3 at Tyr705 and subsequently reduced the levels of STAT3-regulated proteins, Mcl-1, survivin and cylcin D1, in CS-1008-treated HCC cells. Knockdown of STAT3 by RNA interference overcame apoptotic resistance to CS-1008 in HCC cells, and ectopic expression of STAT3 in HCC cells abolished the sensitizing effects of sorafenib and SC-49 on CS-1008-induced apoptosis, indicating that inhibition of STAT3 mediates the enhancing effects of these compounds when combined with CS-1008. Importantly, inhibition of SHP-1 by adding a specific SHP-1 inhibitor reduced the effects of SC-49 and CS-1008 on p-STAT3 and apoptosis, whereas co-treatment of CS-1008 with SC-49 increased the activity of SHP-1. These data indicate that the combined effects of CS-1008 and SC-49 on HCC are mediated by SHP-1. Moreover, the combination of CS-1008 and SC-49 inhibited HCC xenograft tumour growth in vivo. Conclusions and Implications: Sorafenib and its derivative SC-49 sensitize HCC cells to the antitumour effects of CS-1008 through SHP-1-dependent inactivation of STAT3. British Journal of Pharmacology ? 2012 The British Pharmacological Society. | - |
dc.publisher | John Wiley and Sons Inc. | - |
dc.relation.ispartof | British Journal of Pharmacology | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | angiogenesis inhibitor; cyclin D1; protein mcl 1; protein tyrosine phosphatase SHP 1; scandium 49; sorafenib; STAT3 protein; survivin; tigatuzumab; unclassified drug; animal experiment; animal model; animal tissue; antineoplastic activity; apoptosis; article; cancer cell culture; cancer inhibition; carcinoma cell; concentration response; controlled study; down regulation; drug potentiation; drug resistance; drug sensitization; enzyme activity; enzyme inhibition; in vitro study; in vivo study; liver cell carcinoma; male; mouse; nonhuman; priority journal; protein expression; protein phosphorylation; signal transduction; tumor xenograft | - |
dc.title | Sorafenib and its derivative SC-49 sensitize hepatocellular carcinoma cells to CS-1008, a humanized anti-TNFRSF10B (DR5) antibody | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1111/j.1476-5381.2012.02212.x | - |
dc.identifier.scopus | 2-s2.0-84984558781 | - |
dc.relation.pages | 658-672 | - |
dc.relation.journalvolume | 168 | - |
dc.relation.journalissue | 3 | - |
item.openairetype | journal article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.fulltext | no fulltext | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
crisitem.author.dept | Clinical Medicine | - |
crisitem.author.dept | Oncology | - |
crisitem.author.dept | Oncology-NTUH | - |
crisitem.author.orcid | 0000-0001-8316-3785 | - |
crisitem.author.orcid | 0000-0002-9152-6512 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
顯示於: | 臨床醫學研究所 |
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