PPARgamma pathway activation results in apoptosis and COX-2 inhibition in HepG2 cells.
OBJECTIVE
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), ((3)H) 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 PGE(2) was decreased transiently after 12 h of treatment with 30 microM troglitazone.


CONCLUSIONS
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.
Li
Ming-Yi
MY
Department of General Surgery,Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong Province, China. zjmyli@sohu.com
Deng
Hua
H
Zhao
Jia-Ming
JM
Dai
Dong
D
Tan
Xiao-Yu
XY
D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000503:physiopathology*; D051546:Cyclooxygenase 2; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008113:Liver Neoplasms / Q000503:physiopathology*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D008565:Membrane Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases