Troglitazone, a peroxisome proliferator-activated receptor gamma ligand, induces growth inhibition and apoptosis of HepG2 human liver cancer cells.
OBJECTIVE
To examine the effect of troglitazone, a peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand, on the proliferation and apoptosis of human liver cancer cells.


METHODS
Liver cancer cell line HepG2 was cultured and treated with troglitazone. Cell proliferation was detected by 3-(4-,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay; apoptosis was detected by flow cytometry and terminal deoxynucleotidyl transferase-mediated nick end labeling of DNA fragmentation sites (TUNEL) assay; and apoptosis-related protein was detected by immunocytochemistry and Western blotting.


RESULTS
Troglitazone inhibited growth and induced apoptosis of HepG2 cells in a dose-dependent manner, and induced activation of caspase-3 expression. Troglitazone not only drove apoptosis-inhibiting factor survivin to translocate incompletely from the nucleus to the cytoplasm, but also inhibited expression of survivin, while it did not affect expression of apoptosis-promoting factor Bax.


CONCLUSIONS
PPAR gamma ligands inhibit growth and induce apoptosis of liver cancer cells, and may have applications for the prevention and treatment of liver cancer.
Zhou
Yan-Ming
YM
Department of Molecular Oncology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
Wen
Yin-Hao
YH
Kang
Xiao-Yan
XY
Qian
Hai-Hua
HH
Yang
Jia-Mei
JM
Yin
Zheng-Feng
ZF
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D053148:Caspase 3 / Q000096:biosynthesis; D002467:Cell Nucleus / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020287:In Situ Nick-End Labeling; D008024:Ligands; D008954:Models, Biological; D047495:PPAR gamma / Q000378:metabolism*; D021381:Protein Transport; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
D000970:Antineoplastic Agents; D002839:Chromans; D008024:Ligands; D047495:PPAR gamma; D013778:Tetrazolium Salts; D013844:Thiazoles; D045162:Thiazolidinediones; D053148:Caspase 3; C022616:thiazolyl blue; D000077288:Troglitazone