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Inhibition of Autophagy by Deguelin Sensitizes Pancreatic Cancer Cells to Doxorubicin

Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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Academic Editor: Stephen A. Bustin
Int. J. Mol. Sci. 2017, 18(2), 370; https://doi.org/10.3390/ijms18020370
Received: 21 November 2016 / Revised: 4 February 2017 / Accepted: 4 February 2017 / Published: 10 February 2017
(This article belongs to the Section Biochemistry)
Pancreatic cancer is the fourth most common cause of cancer mortality worldwide. Furthermore, patients with pancreatic cancer experience limited benefit from current chemotherapeutic approaches because of drug resistance. Therefore, an effective therapeutic strategy for patients with pancreatic cancer is urgently required. Deguelin is a natural chemopreventive drug that exerts potent antiproliferative activity in solid tumors by inducing cell death. However, the molecular mechanisms underlying this activity have not been fully elucidated. Here we show that deguelin blocks autophagy and induces apoptosis in pancreatic cancer cells in vitro. Autophagy induced by doxorubicin plays a protective role in pancreatic cancer cells, and suppressing autophagy by chloroquine or silencing autophagy protein 5 enhanced doxorubicin-induced cell death. Similarly, inhibition of autophagy by deguelin also chemosensitized pancreatic cancer cell lines to doxorubicin. These findings suggest that deguelin has potent anticancer effects against pancreatic cancer and potentiates the anti-cancer effects of doxorubicin. These findings provide evidence that combined treatment with deguelin and doxorubicin represents an effective strategy for treating pancreatic cancer. View Full-Text
Keywords: pancreatic cancer; deguelin; autophagy; doxorubicin pancreatic cancer; deguelin; autophagy; doxorubicin
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Xu, X.D.; Zhao, Y.; Zhang, M.; He, R.Z.; Shi, X.H.; Guo, X.J.; Shi, C.J.; Peng, F.; Wang, M.; Shen, M.; Wang, X.; Li, X.; Qin, R.Y. Inhibition of Autophagy by Deguelin Sensitizes Pancreatic Cancer Cells to Doxorubicin. Int. J. Mol. Sci. 2017, 18, 370.

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