Gemcitabine Resistance is Associated with Epithelial-Mesenchymal Transition and Induction of HIF-1α in Pancreatic Cancer Cells

Author(s): Rui Wang, Long Cheng, Jun Xia, Zishu Wang, Qiong Wu, Zhiwei Wang

Journal Name: Current Cancer Drug Targets

Volume 14 , Issue 4 , 2014

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Pancreatic cancer is one of the highly aggressive malignant diseases worldwide. To achieve better treatment outcome of pancreatic cancer, in the current study we explore the underlying molecular mechanism of drug resistance in pancreatic cancer cells. We found that resistance to gemcitabine is associated with epithelial-mesenchymal transition (EMT) phenotype in a panel of pancreatic cancer cell lines. Notably, gemcitabine-resistant pancreatic cancer cells acquire EMT phenotype. Moreover, gemcitabine-resistant cells have increased migration and invasion activities. Furthermore, we observed the high expression of HIF-1α in gemcitabine-resistant cells. More importantly, inhibition of HIF-1α in gemcitabine-resistant cells caused partial reversal of EMT phenotype, suggesting that HIF-1α was critically involved in gemcitabine-resistant-mediated EMT. Therefore, targeting HIF-1α could be an effective strategy for the treatment of pancreatic cancer.

Keywords: Chemoresistance, EMT, gemcitabine, HIF-1α, pancreatic cancer.

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Article Details

Year: 2014
Published on: 09 May, 2014
Page: [407 - 417]
Pages: 11
DOI: 10.2174/1568009614666140226114015
Price: $65

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