Naringenin decreases invasiveness and metastasis by inhibiting TGF-β-induced epithelial to mesenchymal transition in pancreatic cancer cells

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...

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Veröffentlicht in:	PloS one 2012-12, Vol.7 (12), p.e50956
Hauptverfasser:	Lou, Changjie, Zhang, Fayun, Yang, Ming, Zhao, Juan, Zeng, Wenfeng, Fang, Xiaocui, Zhang, Yanqiao, Zhang, Chunling, Liang, Wei
Format:	Artikel
Sprache:	eng
Schlagworte:	Apoptosis - drug effects Biology Biophysics Blotting, Western Cadherins Cancer Cancer therapies Cell cycle Cell migration Cell Movement - drug effects Cell Proliferation - drug effects Cytotoxicity Deoxycytidine - analogs & derivatives Deoxycytidine - pharmacology Drug resistance Drug Resistance, Neoplasm - drug effects Embryogenesis Embryonic growth stage Epithelial-Mesenchymal Transition - drug effects Estrogen Antagonists - pharmacology Extracellular matrix Flavanones - pharmacology Gelatinase A Gelatinase B Gemcitabine Gene expression Gene regulation Growth factors Humans Invasiveness Kinases Laboratories Ligands Markers Medicine Mesenchyme Metastases Metastasis mRNA N-Cadherin Naringenin Neoplasm Invasiveness Oncology Pancreatic cancer Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Pancreatic Neoplasms - prevention & control Peptides Pharmaceuticals Phosphorylation - drug effects Physical characteristics Prevention Proteins Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics Signal transduction Signaling Smad3 protein Studies Transforming growth factor Transforming Growth Factor beta - genetics Transforming Growth Factor beta - metabolism Transforming growth factor-b Transforming growth factor-b1 Tumor Cells, Cultured Tumorigenesis Vimentin Wound Healing - drug effects
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Zusammenfassung:	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.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0050956