Gemcitabine resistance is associated with epithelial-mesenchymal transition and induction of HIF-1α in pancreatic cancer cells.

Authors:
Rui Wang
Rui Wang
Laurentian University
Sudbury | Canada
Long Cheng
Long Cheng
Beijing Institute of Biotechnology
China
Jun Xia
Jun Xia
National University of Singapore
Singapore
Zishu Wang
Zishu Wang
Sichuan University
China
Dr. Qiong Wu
Dr. Qiong Wu
Guangdong Pharmaceutical University
Guanghzou | China
Zhiwei Wang
Zhiwei Wang
Harvard Medical School
Israel

Curr Cancer Drug Targets 2014 ;14(4):407-17

Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, China.

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.
January 2015
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