{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:34:07Z","timestamp":1790112847733,"version":"4.0.1"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T00:00:00Z","timestamp":1539561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2016R1D1A1B03932800"],"award-info":[{"award-number":["2016R1D1A1B03932800"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Paclitaxel (PTX) is commonly used to treat urothelial carcinoma (UC) after platinum-based chemotherapy has failed. However, single-agent taxane therapy is not sufficient to inhibit tumor progression and drug resistance in advanced UC. Epithelial-to-mesenchymal transition (EMT) induced by fibroblast growth factor receptor (FGFR)1 signaling has been proposed as a mechanism of PTX resistance, but it is unclear whether this can be overcome by FGFR1 inhibition. The present study investigated whether FGFR1 overexpression contributes to PTX resistance and whether FGFR inhibition can enhance PTX efficacy in UC. The effects of PTX combined with the FGFR inhibitor BGJ398 were evaluated in UC cell lines by flow cytometry; Western blot analysis; cell viability, migration, and colony forming assays; and RNA interference. PTX+BGJ398 induced cell cycle arrest and apoptosis in UC cells with mesenchymal characteristics was accompanied by downregulation of cyclin D1 protein and upregulation of gamma-histone 2A family member X and cleaved poly(ADP-ribose) polymerase. Additionally, PTX+BGJ398 synergistically suppressed UC cell migration and colony formation via regulation of EMT-associated factors, while FGFR1 knockdown enhanced the antitumor effect of PTX. These findings provide a basis for development of effective strategies for overcoming PTX resistance in UC through inhibition of FGFR1 signaling.<\/jats:p>","DOI":"10.3390\/ijms19103164","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T03:43:01Z","timestamp":1539574981000},"page":"3164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["BGJ398, A Pan-FGFR Inhibitor, Overcomes Paclitaxel Resistance in Urothelial Carcinoma with FGFR1 Overexpression"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2292-906X","authenticated-orcid":false,"given":"Se Hyun","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea"},{"name":"Department of Medicine, Graduate School of Yonsei University, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haram","family":"Ryu","sequence":"additional","affiliation":[{"name":"Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam 13605, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan-Young","family":"Ock","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koung Jin","family":"Suh","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Yun","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6426-9074","authenticated-orcid":false,"given":"Ji-Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong-Ok","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keun-Wook","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Mee","family":"Bang","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jee Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Seok","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University 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