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Nutrients 2016, 8(10), 546;

YAP Inhibition by Resveratrol via Activation of AMPK Enhances the Sensitivity of Pancreatic Cancer Cells to Gemcitabine

Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
Department of Anesthesiology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
Authors to whom correspondence should be addressed.
Received: 15 July 2016 / Revised: 15 August 2016 / Accepted: 30 August 2016 / Published: 23 September 2016
(This article belongs to the Special Issue Polyphenols for Cancer Treatment or Prevention)
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Resveratrol, a natural polyphenol present in most plants, inhibits the growth of numerous cancers both in vitro and in vivo. Aberrant expression of YAP has been reported to activate multiple growth-regulatory pathways and confer anti-apoptotic abilities to many cancer cells. However, the role of resveratrol in YES-activated protein (YAP) expression and that of YAP in pancreatic cancer cells’ response to gemcitabine resistance remain elusive. In this study, we found that resveratrol suppressed the proliferation and cloning ability and induced the apoptosis of pancreatic cancer cells. These multiple biological effects might result from the activation of AMP-activation protein kinase (AMPK) (Thr172) and, thus, the induction of YAP cytoplasmic retention, Ser127 phosphorylation, and the inhibition of YAP transcriptional activity by resveratrol. YAP silencing by siRNA or resveratrol enhanced the sensitivity of gemcitabine in pancreatic cancer cells. Taken together, these findings demonstrate that resveratrol could increase the sensitivity of pancreatic cancer cells to gemcitabine by inhibiting YAP expression. More importantly, our work reveals that resveratrol is a potential anticancer agent for the treatment of pancreatic cancer, and YAP may serve as a promising target for sensitizing pancreatic cancer cells to chemotherapy. View Full-Text
Keywords: pancreatic cancer; resveratrol; AMPK; YAP; gemcitabine pancreatic cancer; resveratrol; AMPK; YAP; gemcitabine

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Jiang, Z.; Chen, X.; Chen, K.; Sun, L.; Gao, L.; Zhou, C.; Lei, M.; Duan, W.; Wang, Z.; Ma, Q.; Ma, J. YAP Inhibition by Resveratrol via Activation of AMPK Enhances the Sensitivity of Pancreatic Cancer Cells to Gemcitabine. Nutrients 2016, 8, 546.

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