Published online Jun 15, 2003. doi: 10.3748/wjg.v9.i6.1220
Revised: January 4, 2003
Accepted: January 28, 2003
Published online: June 15, 2003
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 after 12 h of treatment with 30 μM troglitazone.
CONCLUSION: TGZ inhibits cell proliferation and induces apoptosis in HepG2 cells, which may be associated with the activation of caspase-3-like 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.