Effects of activation of peroxisome proliferators-activated receptorγon biological behaviors of human liver tumor cells

Objective To investigate the expression of peroxisome proliferators-activated recep- torγ(PPARγ)and examine the effects of PPARγby its selective ligands on cell growth in human liver tumor cell lines and explore its mechanism.Methods Three human liver tumor cell lines were used to study the expression of PPARγby RT-PCR and western blotting.The effects of PPARγon cell growth were determined by MTT assay,on cell cycle by flow cytometry,on cell cycle regulating fac- tors by RT-PCR and on cell apoptosis by Annexin V-FITC and DAPI staining.Results RT-PCR and western blotting showed that SMMC-7721,Hep G2 and Hep 3B cells expressed PPARγmRNA and protein.PPARγagonists troglitazone and pioglitazone showed a potent dose-response effect in the growth inhibition of the 3 cells lines at the concentration of 25μmol/L.Cell cycle distribution signifi- cantly increased in G,phase and decreased in S phase with increment in dose of the ligands.After u- sing troglitazone of 10,25 and 50μmol/L to treat SMMC-7721 cells for 48 h,cyclin D1 was down- regulated and P21~(WAF1/CIP1)upregulated and there was no marked change in P27~(KIP1).Activation of PPARγalso induced SMMC-7721 cell apoptosis at the concentrations of 25 and 50μmol/L.Conclu- sions SMMC-7721,Hep Gz and Hep 3B cell lines express PPARγ.PPARγagonists significantly in- hibits the growth of the 3 cell lines.The effects might be due to inducing apoptosis and down-regula- ting expression of cyclin D1 and up-regulating P21~(WAF1/CIP1)to result in G,cell arrest.