{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T09:30:54Z","timestamp":1773480654875,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2013,8,6]],"date-time":"2013-08-06T00:00:00Z","timestamp":1375747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2013,10]]},"abstract":"The development of multi\u2010drug resistance (MDR<\/jats:styled-content>) represents a major obstacle in the successful treatment of cancers. However, the factors and mechanisms that lead to MDR<\/jats:styled-content> in cholangiocarcinoma (CCA<\/jats:styled-content>), a chemoresistant bile duct carcinoma with a poor prognosis, remain unclear. In this study, we established a human MDR CCA<\/jats:styled-content> cell line QBC<\/jats:styled-content>939\/5\u2010FU<\/jats:styled-content>. Compared with QBC<\/jats:styled-content>939 cells, a rounder shape, a higher nuclear\u2013cytoplasmic ratio, a shorter cell cycle, faster growth and resistance to chemotherapeutics are major characteristics of QBC<\/jats:styled-content>939\/5\u2010FU<\/jats:styled-content> cells. P\u2010glycoprotein (P\u2010gp) and \u03b2\u2010catenin were upregulated in QBC<\/jats:styled-content>939\/5\u2010FU<\/jats:styled-content> cells. Furthermore, the drug susceptibility of QBC<\/jats:styled-content>939 cells to common chemotherapeutics was significantly decreased after Wnt3a treatment, whereas inhibition of Wnt\/\u03b2\u2010catenin pathway by \u03b2\u2010catenin siRNA<\/jats:styled-content> reversed the MDR<\/jats:styled-content> of QBC<\/jats:styled-content>939\/5\u2010FU<\/jats:styled-content> cells to chemotherapeutics. Molecular study revealed that activation of Wnt\/\u03b2\u2010catenin pathway resulted in upregulation of P\u2010gp and contributed to MDR<\/jats:styled-content> of QBC<\/jats:styled-content>939\/5\u2010FU<\/jats:styled-content> cells. Extraction of Siamese Crocodile 3 (ESC<\/jats:styled-content>\u20103) bile enhanced the drug sensitivity of QBC<\/jats:styled-content>939\/5\u2010FU<\/jats:styled-content> cells to 5\u2010FU<\/jats:styled-content>, paralleled with downregulation of \u03b2\u2010catenin and P\u2010gp. The association of Wnt\/\u03b2\u2010catenin pathway and P\u2010gp was further confirmed by the clinical data for CCA<\/jats:styled-content> tissues. Our study represents the first implication of Wnt\/\u03b2\u2010catenin activation in the MDR<\/jats:styled-content> of CCA<\/jats:styled-content>, which may be a beneficial target for the clinical treatment of CCA<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/cas.12223","type":"journal-article","created":{"date-parts":[[2013,7,3]],"date-time":"2013-07-03T23:26:11Z","timestamp":1372893971000},"page":"1303-1308","source":"Crossref","is-referenced-by-count":92,"title":["Inhibition of Wnt\/\u03b2\u2010catenin signaling downregulates P\u2010glycoprotein and reverses multi\u2010drug resistance of cholangiocarcinoma"],"prefix":"10.1111","volume":"104","author":[{"given":"Dong\u2010Yan","family":"Shen","sequence":"first","affiliation":[{"name":"Center Laboratory The First Affiliated Hospital of Xiamen University Xiamen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xiamen Diabetes Institute The 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