International Journal of Molecular Sciences (Feb 2017)

Inhibition of Autophagy by Deguelin Sensitizes Pancreatic Cancer Cells to Doxorubicin

  • Xiao Dong Xu,
  • Yan Zhao,
  • Min Zhang,
  • Rui Zhi He,
  • Xiu Hui Shi,
  • Xing Jun Guo,
  • Cheng Jian Shi,
  • Feng Peng,
  • Min Wang,
  • Min Shen,
  • Xin Wang,
  • Xu Li,
  • Ren Yi Qin

DOI
https://doi.org/10.3390/ijms18020370
Journal volume & issue
Vol. 18, no. 2
p. 370

Abstract

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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.

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