The Experimental Study On Effects Of Activation Of Peroxisome Proliferator-activated Receptor γ On Human Hepatocellular Carcinoma Cell Lines

Objective: To investigate the expression of peroxisome proliferator -activated receptor γ(PPARγ) in human hepatocellular carcinoma cell lines and the tissue of hepatocellular carcinoma.To investigate the growth inhibition ,apoptosis and the influence on ability of invasion of human hepatocellular carcinoma cell lines by PPARy agonists Troglitazone and Pioglitazone,which can activate PPARγ. Furthermore,we investigate the mechanism of the impact on hepatocellular carcinoma cells.Methods: (1)The expression of PPARγ in in human hepatocellular carcinoma cell lines and the tissue of hepatocellular carcinoma was detected by RT-PCR and Westenblot; (2)The effects of PPARy agonists Troglitazone and Pioglitazone on cells were investigated by MTT and soft agarose clonegenic assays. (3)The effect on invasive ability of hepatocellular carcinoma cell lines by PPARy agonists was detected by Boyden Chamber in vitro. (4)The apoptosis was detected by Annexin V-FITC and DAPI staining. (5)The cell cycle was analyzed by FCM using PI staining and the genes which regulate cell cycle were detected by RT-PCR. We also use RT-PCR to investigate the genes expression involving cells invasion.Results: (1)The expression of PPARy was found in three hepatocellular carcinoma cell lines SMMC-7721,Hep G2, Hep 3B and 8 hepatocellularcarcinoma tissues; ?PPARy agonists Troglitazone and Pioglitazone can greatly inhibit the growth of the three hepatocellular carcinoma cell lines and can also inhibit the bility of invasion by activating PPARy; ?Activation of PPARy resulted in Gl cell cycle arrest in hepatocellular carcinoma cell lines; ?After activation, PPARy down-regulated the expression of Cyclin Dl mRNA and up-regulated P2lWAF1/CIP1 mRNA; ?PPARy agonists Troglitazone and Pioglitazone induced SMMC-7721 apoptosis; ?Activation of PPARy down-regulated the expression of MMP-2 and MMP-9 mRNA .Conclusions: The expression of PPARy was found in three hepatocellular carcinoma cell lines SMMC-7721 > Hep G2^ Hep 3B and 8 hepatocellular carcinoma tissues; PPARy agonists Troglitazone and Pioglitazone can greatly inhibit the growth of the three hepatocellular carcinoma cell lines; Activation of PPARy resulted in Gl cell cycle arrest and induced cell apoptosis in hepatocellular carcinoma cell lines,by which it inhibited cells growth.The mechanism of Gl cell cycle arrest was due to down-regulate the expression of Cyclin Dl and up-regulate P21WAF1/CIP1 ; PPARy agonists significantly inhibited SMMC-7721 the bility of invasion by down-regulating the expression of MMP-2 and MMP-9 .In conclusion, PPARy gene and its agonists provide us a new therapic pathway for hepatocellular carcinoma .