Endocrinol Metab > Volume 24(1); 2009 > Article
Journal of Korean Endocrine Society 2009;24(1):25-32.
DOI: https://doi.org/10.3803/jkes.2009.24.1.25    Published online March 1, 2009.
Effects of Peroxisome Proliferator-Activated Receptor (PPAR) Delta on the Growth and Invasion of a Thyroid Cancer Cell Line.
Won Gu Kim, Hyun Jeung Choi, Eui Young Kim, Tae Yong Kim, Won Bae Kim, Seong Chul Kim, Young Kee Shong
1Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Korea.
2Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Korea.
3Asan Institute of Life Science, Korea.
Abstract
BACKGROUND
Peroxisome proliferator-activated receptor delta (PPAR-delta) is a ligand-activated nuclear transcription factor that is associated with many diseases, such as diabetes, obesity, metabolic syndrome, and cancer. However, the function of PPAR-delta is controversial in carcinogenesis since its ligands may inhibit or promote the growth of cancer cells. The purpose of this study was to determine the effect of GW501516, the specific agonist of PPAR-delta, in the growth and invasiveness of thyroid cancer cell lines by modulation of the target genes, ANGPTL-4 and MCP-1. METHODS: Three kinds of human cancer cell lines, FRO (thyroid anaplastic carcinoma), NPA (melanoma), and ARO (colon cancer) were treated with GW501516 in serum-free media. Cell viability was assayed using a colorimetric cell counting kit-8 assay. The changes in the level of expression of PPAR-delta and its target genes, angiopoietin-like protein-4 (ANGPTL-4) and monocyte chemotactic protein-1 (MCP-1), were determined by RT-PCR analysis and invasiveness was assessed by a cell invasion assay kit. RESULTS: GW501516 inhibited the cell growth of cancer cell lines in a dose-dependent manner and modulated the stimulation of ANGPTL-4, as well as inhibition of MCP-1. These effects were more prominent in NPA and ARO, but less effective in the thyroid cancer cell line, which had higher PPAR-delta and lower ANGPTL-4 mRNA levels. The inhibitory effects of GW501516 on cancer invasiveness had a similar pattern. CONCLUSION: The activation of PPAR-delta by GW501516 reduced the cell growth and invasiveness of the thyroid cancer cell line. This effect of GW501516 was associated with a stimulatory effect of ANGPTL4 and an inhibitory effect of MCP-1 in cancer cell lines. GW501516 was less effective in the thyroid cancer cell line, which had a low basal ANGPTL-4 mRNA level. The findings of our study serve as an impetus for further studies to elucidate the precise role of ANGPTL-4 and PPAR-delta in carcinogenesis.
Key Words: Angiopoietin-like protein-4, Monocyte chemotactic protein-1, Peroxisome proliferator-activated receptor delta, Thyroid cancer


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