{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T01:24:02Z","timestamp":1780622642141,"version":"3.54.1"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,3,12]],"date-time":"2014-03-12T00:00:00Z","timestamp":1394582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Anatomical Record"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Drug\u2010resistance to gemcitabine chemotherapy in pancreatic cancer is still an unsolved problem. Combinations of other chemotherapy drugs with gemcitabine have been shown to increase the efficacy of gemcitabine\u2010based treatment. In this study, the effect of berbamine on the antitumor activity of gemcitabine was evaluated in human pancreatic cancer cell lines Bxpc\u20103 and Panc\u20101, and the underlying mechanisms were explored. Our results demonstrated that berbamine exhibited a time\u2010 and dose\u2010dependent inhibitory effect in the pancreatic cancer cell lines. Berbamine enhanced gemcitabine\u2010induced cell growth inhibition and apoptosis in these cells. Combined treatment of berbamine and gemcitabine resulted in down\u2010regulation of anti\u2010apoptotic proteins (Bcl\u20102, Bcl\u2010xL) and up\u2010regulation of pro\u2010apoptotic proteins (Bax, Bid). More importantly, berbamine treatment in combination with gemcitabine activated the transforming growth factor\u2010\u03b2\/Smad (TGF\u2010\u03b2\/Smad) signaling pathway, as a result of a decrease in Smad7 and an increase in transforming growth factor\u2010\u03b2 receptor II (T\u03b2RII) expression. Changes in downstream targets of Smad7, such as up\u2010regulation of p21 and down\u2010regulation of c\u2010Myc and Cyclin D1 were also observed. Therefore, berbamine could enhance the antitumor activity of gemcitabine by inhibiting cell growth and inducing apoptosis, possibly through the regulation of the expression of apoptosis\u2010related proteins and the activation of TGF\u2010\u03b2\/Smad signaling pathway. Our study indicates that berbamine may be a promising candidate to be used in combination with gemcitabine for pancreatic cancer treatment. Anat Rec, 297:802\u2013809, 2014. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ar.22897","type":"journal-article","created":{"date-parts":[[2014,6,9]],"date-time":"2014-06-09T05:24:54Z","timestamp":1402291494000},"page":"802-809","source":"Crossref","is-referenced-by-count":21,"title":["Berbamine Enhances the Antineoplastic Activity of Gemcitabine in Pancreatic Cancer Cells by Activating Transforming Growth Factor\u2010\u03b2\/Smad Signaling"],"prefix":"10.1002","volume":"297","author":[{"given":"Xiaoli","family":"Jin","sequence":"first","affiliation":[{"name":"Department of General Surgery Sir Run Run Shaw Hospital, School of Medicine Zhejiang University  Hangzhou China 310009"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulian","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of General Surgery the Second Affiliated Hospital, School of Medicine, Zhejiang University  Hangzhou China 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