t-0070907 and Esophageal-Neoplasms

Topics: Adenocarcinoma; Animals; Benzamides; Cell Line, Tumor; Cell Survival; DNA-Binding Proteins; Enhancer Elements, Genetic; Esophageal Neoplasms; Fatty Acids; GATA6 Transcription Factor; Gene Expression Regulation, Neoplastic; Humans; Kruppel-Like Transcription Factors; Male; Mice, Nude; PPAR gamma; Promoter Regions, Genetic; Proto-Oncogene Proteins c-ets; Pyridines; Transcription Factors; Xenograft Model Antitumor Assays

Esophageal cancer is difficult to treat because of its rapid progression, and more effective therapeutic approaches are needed. The PPARgamma is a nuclear receptor superfamily member that is expressed in many cancers. PPARgamma expression is a feature of esophageal cancer cell lines, and in the present investigation, the PPARgamma antagonists T0070907 and GW9662 could induce loss of invasion but could not induce growth reduction or apoptosis at low concentrations (< 10 mM). A high concentration of antagonists (50 microM) inhibited cell growth and induced apoptosis, but these effects did not explain our result at the low concentration. Morphological change, decreased expression of the cell signaling pathway and inhibition of cancer cell invasion were observed in the low concentration. This suggested that PPARgamma antagonists inhibited esophageal cancer cell invasion as well as cell adherence, most likely due to alteration in the FAK-MAPK pathway, and this was independent of apoptosis. These results suggested that PPARgamma plays an important role in cancer cell invasion and that it might be a novel target for therapy of esophageal cancer.

Topics: Actins; Anilides; Apoptosis; Benzamides; Blotting, Western; Cell Adhesion; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Esophageal Neoplasms; Extracellular Matrix; Extracellular Signal-Regulated MAP Kinases; Fluorescent Antibody Technique; Focal Adhesion Protein-Tyrosine Kinases; Humans; Neoplasm Invasiveness; Phosphorylation; PPAR gamma; Pyridines