{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:33:53Z","timestamp":1790303633681,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2019,6,30]],"date-time":"2019-06-30T00:00:00Z","timestamp":1561852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005762","name":"National Taiwan University Hospital","doi-asserted-by":"publisher","award":["108-4104, 108-M4137, and 107-S3784"],"award-info":[{"award-number":["108-4104, 108-M4137, and 107-S3784"]}],"id":[{"id":"10.13039\/501100005762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["107-2321-B-008-001 and 107-2314-B-002-268-MY2"],"award-info":[{"award-number":["107-2321-B-008-001 and 107-2314-B-002-268-MY2"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"New Taipei City Hospital","award":["108"],"award-info":[{"award-number":["108"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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-resistant UC cells (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\u201345 \u03bcM) 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.<\/jats:p>","DOI":"10.3390\/ijms20133218","type":"journal-article","created":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T03:23:59Z","timestamp":1561951439000},"page":"3218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"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"],"prefix":"10.3390","volume":"20","author":[{"given":"Kuan-Lin","family":"Kuo","sequence":"first","affiliation":[{"name":"Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 100, Taiwan"},{"name":"Department of Urology, College of Medicine, National Taiwan University, Taipei 100, Taiwan"},{"name":"Department of Urology, National Taiwan University Hospital, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9976-1197","authenticated-orcid":false,"given":"Shing-Hwa","family":"Liu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 100, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan"},{"name":"Department of Pediatrics, National Taiwan University Hospital, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Chou","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Taiwan University Hospital, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4586-7308","authenticated-orcid":false,"given":"Fu-Shun","family":"Hsu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan"},{"name":"Department of Urology, New Taipei City Hospital, New Taipei City 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Ming","family":"Chow","sequence":"additional","affiliation":[{"name":"Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 100, Taiwan"},{"name":"Department of Urology, College of Medicine, National Taiwan University, Taipei 100, Taiwan"},{"name":"Department of Urology, National Taiwan University Hospital, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Wei","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Urology, College of Medicine, National Taiwan University, Taipei 100, Taiwan"},{"name":"Department of Urology, National Taiwan University Hospital, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4721-7296","authenticated-orcid":false,"given":"Shao-Ping","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology, College of Medicine, National Taiwan University, Taipei 100, Taiwan"},{"name":"Department of Urology, National Taiwan University Hospital, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5548-7675","authenticated-orcid":false,"given":"Chung-Sheng","family":"Shi","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Hsun","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Urology, College of Medicine, National Taiwan University, Taipei 100, Taiwan"},{"name":"Department of Urology, National Taiwan University Hospital, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Ming","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Urology, College of Medicine, National Taiwan University, Taipei 100, Taiwan"},{"name":"Department of Urology, National Taiwan University Hospital, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Chiang","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Urology, College of Medicine, National Taiwan University, Taipei 100, Taiwan"},{"name":"Department of Urology, National Taiwan University Hospital, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0989-0578","authenticated-orcid":false,"given":"Kuo-How","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Urology, College of Medicine, National Taiwan University, Taipei 100, Taiwan"},{"name":"Department of Urology, National Taiwan University Hospital, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,30]]},"reference":[{"key":"ref_1","unstructured":"American Cancer Society (2019, June 29). 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