Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Antimetabolites, Antineoplastic / pharmacology*
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Biomarkers / metabolism
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Cell Adhesion / drug effects
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Survival / drug effects
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Deoxycytidine / analogs & derivatives*
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Deoxycytidine / pharmacology
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Drug Resistance, Neoplasm*
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Epithelial-Mesenchymal Transition / drug effects*
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Gemcitabine
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / agonists*
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Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Neoplasm Invasiveness
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Neoplasm Proteins / agonists
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Pancreatic Neoplasms / drug therapy*
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / pathology
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RNA Interference
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RNA, Small Interfering
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Up-Regulation / drug effects*
Substances
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Antimetabolites, Antineoplastic
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Biomarkers
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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Neoplasm Proteins
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RNA, Small Interfering
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Deoxycytidine
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Gemcitabine