Ubiquitination of p53 is Involved in Troglitazone Induced Apoptosis in Cervical Cancer Cells

Abstract

Peroxisome proliferator-activated receptor gamma (PPAR-γ), a ligand-dependent nuclear transcription factor,has been found to widely exist in tumor tissues and plays an important role in affecting tumor cell growth. Inthis study, we investigated the effect of PPAR-γ on aspects of the cervical cancer malignant phenotype, such ascell proliferation and apoptosis. Cell growth assay, Western blotting, Annexin V and flow cytometry analysisconsistently showed that treatment with troglitazone (TGZ, a PPAR-γ agonist) led to dose-dependent inhibition ofcervical cancer cell growth through apoptosis, whereas T0070907 (another PPAR-γ antagonist???) had no effecton Hela cell proliferation and apoptosis. Furthermore, we also detected the protein expression of p53, p21 andMdm2 to explain the underlying mechanism of PPAR-γ on cellular apoptosis. Our work, finally, demonstratedthe existence of the TGZ-PPAR-γ-p53 signaling pathway to be a critical regulator of cell apoptosis. These resultssuggested that PPAR-γ may be a potential therapeutic target for cervical cancer.

Keywords