https://scholars.lib.ntu.edu.tw/handle/123456789/189804
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor | 內科 | en |
dc.contributor.author | TAI, WEI-TIEN | en |
dc.contributor.author | CHENG, ANN-LII | en |
dc.contributor.author | SHIAU, CHUNG-WAI | en |
dc.contributor.author | HUANG, HSIANG-PO | en |
dc.contributor.author | HUANG, JUI-WEN | en |
dc.contributor.author | CHEN, PEI-JER | en |
dc.contributor.author | CHEN, KUEN-FENG | en |
dc.contributor.author | 鄭安理 | zh-tw |
dc.contributor.author | 陳培哲 | zh-tw |
dc.creator | 戴瑋恬;鄭安理;蕭崇瑋;黃祥博;黃瑞雯;陳培哲 | zh-tw |
dc.creator | TAI, WEI-TIEN;CHENG, ANN-LII;SHIAU, CHUNG-WAI;HUANG, HSIANG-PO;HUANG, JUI-WEN;CHEN, PEI-JER;CHEN, KUEN-FENG | en |
dc.date | 2011 | en |
dc.date.accessioned | 2012-07-05T11:46:48Z | - |
dc.date.accessioned | 2018-07-11T06:26:17Z | - |
dc.date.available | 2012-07-05T11:46:48Z | - |
dc.date.available | 2018-07-11T06:26:17Z | - |
dc.date.issued | 2011 | - |
dc.identifier.uri | http://ntur.lib.ntu.edu.tw//handle/246246/240771 | - |
dc.description.abstract | Background& Aims: Recently, we reported that sorafenib sensitizes hepatocellular carcinoma (HCC) cells to TRAIL through the inhibition of signal transducer and activator of transcription 3 (STAT3). Here, we report that sorafenib inhibits HCC via a kinase-independent mechanism: SHP -1 dependent STAT3 inactivation. Methods: SC-1 is a sorafenib derivative that closely resembles sorafenib structurally but with no kinase inhibition activity. HCC cell lines (PLC5, Huh-7, Hep3B, and Sk-Hep1) were treated with sorafenib or SC-1 and apoptosis and signal transduction were analyzed. In vivo efficacy was determined in nude mice with Huh-7 xenografts. Results: SC-1 showed similar effects to sorafenib on growth inhibition and apoptosis in all tested HCC cell lines. SC-1 down-regulated phosphorylation of phospho-STAT3 (p-STAT3) at tyrosine 705 in all tested HCC cells. Expression of STAT3- driven genes, including Cyclin D1 and Survivin, was also repressed by SC-1. Luciferase reporter assay confirmed the inhibition of transcriptional activity of STAT3 in both sorafenib- treated and SC-1-treated cells. Ectopic expression of STAT3 in PLC5 cells abolished apoptosis in SC-1-treated cells. Sorafenib and SC-1 up-regulated SHP-1 activity. Knockdown of SHP-1, but not SHP-2 or PTP-1B, by small interference RNA reduced apoptosis induced by SC-1. | en |
dc.language | en-us | en |
dc.language.iso | en_US | - |
dc.relation | Journal of Hepatology v.55 pp.1041-1048 | en |
dc.relation.ispartof | Journal of Hepatology | - |
dc.title | Signal transducer and activator of transcription 3 is a major kinase- independent target of sorafenib in hepatocellular carcinoma=STAT3為 Sorafenib於肝癌的主要標的 | en |
dc.relation.pages | 1041-1048 | - |
dc.relation.journalvolume | v.55 | - |
item.languageiso639-1 | en_US | - |
item.grantfulltext | none | - |
item.fulltext | no fulltext | - |
顯示於: | 醫學系 |
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