Thiazolidinediones inhibit cell growth of human oral squamous cell carcinoma in vitro independent of peroxisome proliferator-activated receptor gamma.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. Recently, we have demonstrated that PPARgamma is expressed in human salivary gland tumors and its ligands inhibit the growth of cultured salivary gland cancer cells. However, expression and function of PPARgamma in normal and neoplastic human oral squamous epithelium remains unclear. In the present study, we examined PPARgamma expression in human oral squamous cell carcinoma (OSCC) and tested its ligands for any antitumor effect. PPARgamma mRNA was detected by RT-PCR in some OSCC tissues and cultured cells, but the PPARgamma protein showed neither expression nor ligand-induced transcriptional activity. Despite loss of PPARgamma function, synthetic PPARgamma ligands caused significant dose-dependent inhibition of cancer cell growth. These results suggest that PPARgamma function is inactivated in OSCC cells and the anti-proliferative effect of its synthetic ligands is independent of PPARgamma.