https://scholars.lib.ntu.edu.tw/handle/123456789/431124
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Kuo K.-L. | en_US |
dc.contributor.author | SHING-HWA LIU | en_US |
dc.contributor.author | WEI-CHOU LIN | en_US |
dc.contributor.author | Hsu F.-S. | en_US |
dc.contributor.author | PO-MING CHOW | en_US |
dc.contributor.author | Chang Y.-W. | en_US |
dc.contributor.author | Yang S.-P. | en_US |
dc.contributor.author | Shi C.-S. | en_US |
dc.contributor.author | Hsu C.-H. | en_US |
dc.contributor.author | Liao S.-M. | en_US |
dc.contributor.author | HONG-CHIANG CHANG | en_US |
dc.contributor.author | KUO-HOW HUANG | en_US |
dc.creator | Kuo K.-L.;Shing-Hwa Liu;Lin W.-C.;Hsu F.-S.;Chow P.-M.;Chang Y.-W.;Yang S.-P.;Shi C.-S.;Hsu C.-H.;Liao S.-M.;Chang H.-C.;Huang K.-H. | - |
dc.date.accessioned | 2019-11-12T07:36:15Z | - |
dc.date.available | 2019-11-12T07:36:15Z | - |
dc.date.issued | 2019 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85069263170&doi=10.3390%2fijms20133218&partnerID=40&md5=98d12fc6531022042fbd8abf874df3eb | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/431124 | - |
dc.description.abstract | Cisplatin-based chemotherapy is the primary treatment for metastatic bladder urothelial carcinoma (UC). Most patients inevitably encounter drug resistance and resultant disease relapse. Reduced apoptosis plays a critical role in chemoresistance. Trifluoperazine (TFP), an antipsychotic agent, has demonstrated antitumor effects on various cancers. This study investigated the efficacy of TFP in inhibiting cisplatin-resistant bladder UC and explored the underlying mechanism. Our results revealed that cisplatin-resistantUCcells (T24/R) upregulated the antiapoptotic factor, B-cell lymphoma-extra large (Bcl-xL). Knockdown of Bcl-xL by siRNA resensitized cisplatin-resistant cells to the cisplatin cytotoxic effect. TFP (10–45 μM) alone elicited dose-dependent cytotoxicity, apoptosis, and G0/G1 arrest on T24/R cells. Co-treatment of TFP potentiated cisplatin-induced cytotoxicity in T24/R cells. The phenomenon that TFP alleviated cisplatin resistance to T24/R was accompanied with concurrent suppression of Bcl-xL. In vivo models confirmed that TFP alone effectively suppressed the T24/R xenograft in nude mice. TFP co-treatment enhanced the antitumor effect of cisplatin on the T24/R xenograft. Our results demonstrated that TFP effectively inhibited cisplatin-resistant UCs and circumvented cisplatin resistance with concurrent Bcl-xL downregulation. These findings provide a promising insight to develop a therapeutic strategy for chemoresistant UCs. ? 2019 by the authors. Licensee MDPI, Basel, Switzerland. | - |
dc.language.iso | English | - |
dc.publisher | MDPI AG | - |
dc.relation.ispartof | International Journal of Molecular Sciences | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | caspase 4; cisplatin; cyclin dependent kinase inhibitor; fluorescein isothiocyanate; neuroleptic agent; protein bcl xl; protein p21; protein p27; trifluoperazine; antineoplastic agent; cisplatin; neuroleptic agent; protein bcl x; trifluoperazine; animal cell; animal experiment; animal model; antiapoptotic activity; antineoplastic activity; apoptosis; apoptosis assay; Article; cell culture; cell stress; cell viability; cell viability assay; chemotherapy; cisplatin resistant urothelial carcinoma cell; cisplatin-resistant cell line; cytotoxicity; DNA damage; down regulation; endoplasmic reticulum stress; flow cytometry; gene knockdown; genetic transfection; in vitro study; in vivo study; mouse; MTT assay; nonhuman; percentage of cells in G0/G1 phase; protein expression; T24 cell line; transitional cell carcinoma; tumor volume; upregulation; Western blotting; xenograft; animal; bladder tumor; carcinoma; cell line; drug effect; drug resistance; genetics; human; metabolism; pathology; urothelium; Animals; Antineoplastic Agents; Antipsychotic Agents; Apoptosis; bcl-X Protein; Carcinoma; Cell Line; Cisplatin; Down-Regulation; Drug Resistance, Neoplasm; Humans; Mice; Trifluoperazine; Urinary Bladder Neoplasms; Urothelium | - |
dc.title | Trifluoperazine, an antipsychotic drug, effectively reduces drug resistance in cisplatin-resistant urothelial carcinoma cells via suppressing bcl-xl: An in vitro and in vivo study | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.3390/ijms20133218 | - |
dc.identifier.pmid | 31262032 | - |
dc.identifier.scopus | 2-s2.0-85069263170 | - |
dc.relation.journalvolume | 20 | - |
dc.relation.journalissue | 13 | - |
item.openairetype | journal article | - |
item.fulltext | no fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.grantfulltext | none | - |
item.languageiso639-1 | English | - |
item.cerifentitytype | Publications | - |
crisitem.author.dept | Toxicology | - |
crisitem.author.dept | Pathology | - |
crisitem.author.dept | Pathology-NTUH | - |
crisitem.author.dept | Urology | - |
crisitem.author.dept | Urology-NTUH | - |
crisitem.author.dept | Urology-NTUH | - |
crisitem.author.dept | Urology | - |
crisitem.author.dept | Urology-NTUH | - |
crisitem.author.dept | Surgical Oncology-NTUCC | - |
crisitem.author.orcid | 0000-0002-9976-1197 | - |
crisitem.author.orcid | 0000-0003-2857-3479 | - |
crisitem.author.orcid | 0000-0002-3183-1830 | - |
crisitem.author.orcid | 0000-0001-5411-6680 | - |
crisitem.author.orcid | 0000-0002-0989-0578 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | National Taiwan University Cancer Center (NTUCC) | - |
顯示於: | 毒理學研究所 |
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