Abstract
Abstract Peroxisome proliferator-activated receptor delta (PPARdelta) is a nuclear transcription factor that is recently implicated in tumorigenesis. Previous studies from our lab have shown that PPARdelta activation increases the growth of human hepatocellular carcinoma (HCC) cell lines (Hep 3B, Huh7 and HepG2). The current study was designed to investigate the relationship between PPARdelta activation and STAT3 signaling pathway in human HCC cells. Our data showed that PPARdelta overexpression or activation by its pharmacological ligand (GW501516) significantly increased STAT3-mediated transcriptional activity in Hep3B cells, as determined by luciferease reporter activity assay; this effect is dose-dependent (p<0.01). In contrast, depletion of PPARdelta by its siRNA in Hep3B cells significantly reduced GW501516-induced STAT3 transcriptional activity. PPARdelta overexpression or GW501516 treatment increased the expression of STAT3 protein and induced the translocation of STAT3 from cytosol to nuclei in Hep3B cells. Additionally, PPARdelta overexpression or GW501516 treatment also increased the binding of PPARdelta to STAT3-responsive element through the release of transcriptional repressor Bcl-6. Moreover, overexpression of PPARdelta upregulated the expression of several STAT3 downstream anti-apoptotic molecules including Mcl-1, Suvivin and Bcl-XL. These findings reveal a cross-talk between PPARdelta and STAT3 signaling pathway for human HCC cell growth and such an interaction may play important role in hepatocarcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1018. doi:10.1158/1538-7445.AM2011-1018
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