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
Adenocarcinoma/genetics,metabolism,pathology
Antigens, Differentiation/biosynthesis,genetics
Antigens, Neoplasm/biosynthesis,genetics
Antineoplastic Agents/pharmacology
Blotting, Western
Carcinoma/genetics,metabolism,pathology
Cell Cycle/drug effects
Cell Differentiation/drug effects
Cell Division/drug effects
Cyclin-Dependent Kinase Inhibitor p21
Cyclins/biosynthesis,genetics
Gene Expression Regulation, Neoplastic/drug effects
Growth Inhibitors/pharmacology
Humans
Ligands
Neoplasm Proteins/biosynthesis,drug effects,genetics
Pancreatic Neoplasms/genetics,metabolism,pathology
Receptors, Cytoplasmic and Nuclear/biosynthesis,drug effects,genetics,physiology
Reverse Transcriptase Polymerase Chain Reaction
Thiazoles/pharmacology
Thiazolidinediones
Transcription Factors/biosynthesis,drug effects,genetics,physiology
Tumor Cells, Cultured/drug effects,metabolism,pathology
Tumor Stem Cell Assay
Chemicals
Antigens, Differentiation
Antigens, Neoplasm
Antineoplastic Agents
CDKN1A protein, human
Cyclin-Dependent Kinase Inhibitor p21
Cyclins
Growth Inhibitors
Ligands
Neoplasm Proteins
Receptors, Cytoplasmic and Nuclear
Thiazoles
Thiazolidinediones
Transcription Factors
2,4-thiazolidinedione
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Elnemr A
Department of Surgery II, School of Medicine, Kanazawa University, Kanazawa 920-0934, Japan. aymann1@yahoo.com
Ohta T
Iwata K
Ninomia I
Fushida S
Nishimura G
Kitagawa H
Kayahara M
Yamamoto M
Terada T
Miwa K