Antitumor effects of peroxisome proliferator activate receptor γ ligands on anaplastic thyroid carcinoma

Anaplastic thyroid carcinoma is an aggressive neoplasm and resistant to all sorts of treatment due to its rapid growth and invasive potential. Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor modulating variety of biological properties, such as regulating of adipogenesis, inhibition of cancer cell proliferation or differentiation of tumor cells. The purpose of this study was to evaluate the possibility for the therapeutic effect of PPARγ ligands against anaplastic thyroid tumor in vitro. Expressions of the PPARc gene and protein were examined in 5 human anaplastic carcinoma cell lines (MSA, IAA, ROA, K119 and KOA-2). We next evaluated the effects of PPARγ ligands (Thiazolidinedione, Prostaglandin J2 and RS1303) on proliferation, differentiation, apoptosis and invasion. Five cell lines showed higher level of the PPARc gene and protein expression than papillary thyroid carcinoma. PPARγ ligands inhibited cell proliferation by inducing apoptosis instead of differentiation in dose-dependent manner. PPARγ ligands also down regulated the invasive potential of 5 cell lines. The inhibitory effect of proliferation or invasion was prominent in 3 cell lines, which exhibited higher expression level of the PPARc gene or protein. Our results indicated that PPARγ ligands modify malignant potential of anaplastic carcinoma cell lines altering growth or invasive properties, suggesting that PPARγ could be potentially the novel molecular target for human thyroid anaplastic carcinoma.