Abstract
The aim of this study was to examine whether a specific PPARgamma ligand can inhibit the growth of human pancreatic cancer cells through induction of terminal differentiation. PPARgamma was expressed in five human pancreatic cancer cell lines: Capan-1, AsPC-1, BxPC-3, PANC-1, and MIA PaCa-2. Treatment of these cells with a specific PPARgamma ligand, thiazolidinedione (TZD), resulted in inhibition of both cellular and clonogenic growth, and G1 cell cycle arrest. Finally, thiazolidinedione treatment resulted in induction of p21WAF-1 and increased expression of differentiation markers. These results suggest that thiazolidinedione treatment inhibits growth and induces cellular differentiation in pancreatic cancer cells and thereby reduces their development in favor of differentiated and stable cell phenotype.
MeSH terms
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Adenocarcinoma / genetics
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology*
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Antigens, Differentiation / biosynthesis*
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Antigens, Differentiation / genetics
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Antigens, Neoplasm / biosynthesis*
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Antigens, Neoplasm / genetics
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Antineoplastic Agents / pharmacology*
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Blotting, Western
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Carcinoma / genetics
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Carcinoma / metabolism
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Carcinoma / pathology
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Cell Cycle / drug effects
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Cell Differentiation / drug effects
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Cell Division / drug effects
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / biosynthesis
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Cyclins / genetics
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Gene Expression Regulation, Neoplastic / drug effects*
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Growth Inhibitors / pharmacology*
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Humans
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Ligands
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / drug effects*
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Neoplasm Proteins / genetics
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Pancreatic Neoplasms / genetics
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / pathology*
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Receptors, Cytoplasmic and Nuclear / biosynthesis
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Receptors, Cytoplasmic and Nuclear / drug effects*
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / physiology
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Reverse Transcriptase Polymerase Chain Reaction
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Thiazoles / pharmacology*
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Thiazolidinediones*
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Transcription Factors / biosynthesis
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Transcription Factors / drug effects*
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Transcription Factors / genetics
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Transcription Factors / physiology
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / metabolism
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Tumor Cells, Cultured / pathology
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Tumor Stem Cell Assay
Substances
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Antigens, Differentiation
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Antigens, Neoplasm
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Antineoplastic Agents
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CDKN1A protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Growth Inhibitors
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Ligands
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Neoplasm Proteins
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Receptors, Cytoplasmic and Nuclear
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Thiazoles
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Thiazolidinediones
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Transcription Factors
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2,4-thiazolidinedione