PPARγ pathway activation results in apoptosis and COX－2 inhibition in HepG2 cells

AIM: To investigate whether troglitazone (TGZ), the peroxisome proliferator-activated receptor (PPAR) gamma ligand, can induce apoptosis and inhibit cell proliferation in human liver cancer cell line HepG2 and to explore the molecular mechanisms.METHODS: [3-(4,5)-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT), [^3H] Thymidine incorporation,Hochest33258 staining, DNA ladder, enzyme-linked immunosorbent assay (ELISA), RT-PCR, Northern and Western blotting analyses were employed to investigate the effect of TGZ on HepG2 cells and related molecular mechanisms.RESULTS: TGZ was found to inhibit the growth of HepG2 cells and to induce apoptosis. During the process, the expression of COX-2 mRNA and protein and Bcl-2 protein was down-regulated, while that of Bax and Bak proteins was up-regulated, and the activity of caspase-3 was elevated.Furthermore, the level of PGE2 was decreased transiently alter 12 h of treatment with 30 pM troglitazone.CONCLUSION: TGZ inhibits cell proliferation and induces apoptosis in HepG2 cells, which may be associated with the activation of caspase-3-1ike proteases, down-regulation of the expression of COX-2 mRNA and protein, Bcl-2 protein,the elevation of PGE2 levels, and up-regulation of the expressions of Bax and Bak proteins,