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AIM:To investigate whether troglitazone (TGZ),theperoxisome proliferator-activated receptor (PPAR) gammaligand,can induce apoptosis and inhibit cell proliferation inhuman liver cancer cell line HepG2 and to explore themolecular mechanisms.METHODS:[3-(4,5)-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT),[~3H] Thymidine incorporation,Hochest33258 staining,DNA ladder,enzyme-linkedimmunosorbent assay (ELISA),RT-PCR,Northern andWestern blotting analyses were employed to investigatethe effect of TGZ on HepG2 cells and related molecularmechanisms.RESULTS:TGZ was found to inhibit the growth of HepG2cells and to induce apoptosis.During the process,theexpression of COX-2 mRNA and protein and Bcl-2 proteinwas down-regulated,while that of Bax and Bak proteinswas up-regulated,and the activity of caspase-3 was elevated.Furthermore,the level of PGE_2 was decreased transientlyafter 12 h of treatment with 30 μM troglitazone.CONCLUSION:TGZ inhibits cell proliferation and inducesapoptosis in HepG2 cells,which may be associated with theactivation of caspase-3-1ike proteases,down-regulation ofthe expression of COX-2 mRNA and protein,Bcl-2 protein,the elevation of PGE2 levels,and up-regulation of theexpressions of Bax and Bak proteins,
AIM: To investigate whether troglitazone (TGZ), the perforxisome proliferator-activated receptor (PPAR) gammaligand, can induce apoptosis and inhibit cell proliferation in human liver cancer cell line HepG2 and to explore their molecular mechanisms. METHODS: [3- (4,5) - Thymidine incorporation, Hochest 33258 staining, DNA ladder, enzyme-linked immunosorbent assay (ELISA), RT-PCR, Northern and western blotting analyzes were employed to investigatethe 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. The process of 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. Frthermore, the level of PGE_2 was decreased transiently after 12 h of treatment with 30 μM troglitazone. CONCLUSION: TGZ inhibits cell proliferation and inducesapoptosis in The down-regulation of the expression of COX-2 mRNA and protein, the elevation of PGE2 levels, and up-regulation of theexpressions of Bax and Bcl-2 protein may be associated with theactivation of caspase- Bak proteins,