Abstract
Epithelial to mesenchymal transition (EMT) promotes cellular motility, invasiveness and metastasis during embryonic development and tumorigenesis. Transforming growth factor-β (TGF-β) signaling pathway is a key regulator of EMT. A lot of evidences suggest that this process is Smad3-dependent. Herein we showed that exposure of aspc-1 and panc-1 pancreatic cancer cells to TGF-β1 resulted in characteristic morphological alterations of EMT, and enhancement of cell motility and gemcitabine (Gem) resistance along with an up-regulation of EMT markers genes such as vimentin, N-cadherin, MMP2 and MMP9. Naringenin (Nar) down-regulated EMT markers expression in both mRNA and protein levels by inhibiting TGF-β1/Smad3 signal pathway in the pancreatic cancer cells. Consequently, Nar suppressed the cells migration and invasion and reversed their resistance to Gem.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Blotting, Western
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Cell Movement / drug effects*
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Cell Proliferation / drug effects
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Deoxycytidine / analogs & derivatives
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Deoxycytidine / pharmacology
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Drug Resistance, Neoplasm / drug effects
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Epithelial-Mesenchymal Transition / drug effects*
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Estrogen Antagonists / pharmacology*
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Flavanones / pharmacology*
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Gemcitabine
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Humans
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Neoplasm Invasiveness
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / pathology
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Pancreatic Neoplasms / prevention & control*
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Phosphorylation / drug effects
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism*
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Tumor Cells, Cultured
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Wound Healing / drug effects
Substances
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Estrogen Antagonists
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Flavanones
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RNA, Messenger
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Transforming Growth Factor beta
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Deoxycytidine
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naringenin
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Gemcitabine
Grants and funding
This work was supported by the National Nature Sciences Foundation of China (81173633), grants from State Key Development Plan Project (2011CB707705), the Research Foundation of Department of Health of Heilongjiang Province(2010-107) and the startup Fund of The Affiliated Third Hospital of Harbin Medical University (JJ2010-15). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.