AIM:To investigate the expression of TNF-related apoptosis-inducing Ligand (TRAIL) receptors and antitumor effectsof TRAIL in hepatocellular carcinoma (HCC).METHODS:Expression of TRAIL receptors was determinedin 60 HCC tissues,20 normal liver samples and two HCC celllines (HepG2 and SMMC-7721).The effects of TRAIL onpromoting apoptosis in HCC cell lines were analyzed afterthe cells were exposed to the recombinant TRAIL protein,as well as transfected with TRAIL-expression construct.Invivo effects of TRAIL on tumor growth were investigated byusing nude mice HCC model of hepG2.RESULTS:Both death receptors were expressed in all HCCtissues and normal hepatic samples.In contrast,54 HCCtissues did not express DcR1 and 25 did not express DcR2.But both DcR were detectable in all of the normal liver tissues.The expression patterns of DR and DcR in HCC samples(higher DR expression level and lower DcR expression level)were quite different from those in normal tissue.DR5,DR4,and DcR2 expressed in both cell lines,while no DcR1expression was detected.Recombinant TRAIL alone wasfound to have a slight activity as it killed a maximum of 15%of HCC cells within 24 h.Transfection of the TRAIL cDNAfailed to induce extensive apoptosis in HCC lines.In vivoadministration of TRAIL gene could not inhibit tumor growthin nude mice HCC model.However,chemotherapeutic agentsor anticancer cytokines dramatically augmented TRAIL-induced apoptosis in HCC cell lines.CONCLUSION:Loss of DcR (especially DcR1) in HCC maycontribute to antitumor effects of TRAIL to HCC.HCC isinsensitive towards TRAIL-mediated apoptosis,suggestingthat the presence of mediators can inhibit the TRAIL cell-death-inducing pathway in HCC.TRAIL and chemotherapeuticagents or anticancer cytokines combination may be a novelstrategy for the treatment of HCC. AIM: To investigate the expression of TNF-related apoptosis-inducing Ligand (TRAIL) receptors and antitumor effects of TRAIL in hepatocellular carcinoma (HCC). METHODS: Expression of TRAIL receptors was determined in 60 HCC tissues, 20 normal liver samples and two HCC celllines HepG2 and SMMC-7721). The effects of TRAIL onpromoting apoptosis in HCC cell lines were analyzed afterthe cells were exposed to the recombinant TRAIL protein, as well as transfected with TRAIL-expression construct. Vivo effects of TRAIL on tumor growth were investigated byusing nude mice HCC model of hepG2.RESULTS: Both death receptors were expressed in all HCCtissues and normal hepatic samples. In contrast, 54 HCCtissues did not express DcR1 and 25 did not express DcR2.But both DcR were detectable in all of the normal liver tissues. The expression patterns of DR and DcR in HCC samples (higher DR expression level and lower DcR expression level) were quite different from those in normal tissue. DR5, DR4, and DcR2 expressed in b oth cell lines, while no DcR1expression was detected. Recombinant TRAIL alone wasfound to have a slight activity as it killed a maximum of 15% of HCC cells within 24 h. Transfection of the TRAIL cDNA failed to detect extensive apoptosis in HCC lines. vivoadministration of TRAIL gene could not inhibit tumor growth in nude mice HCC model. Despite, chemotherapeutic agents a anticancer cytokines dramatic augmented TRAIL-induced apoptosis in HCC cell lines. CONCLUSION: Loss of DcR (especially DcR1) in HCC may contribute to antitumor effects of TRAIL to HCC. HCC isinsensitive toward TRAIL-mediated apoptosis, suggesting that the presence of mediators can inhibit the TRAIL cell-death-inducing pathway in HCC. TRAIL and chemotherapeutic agents or anticancer cytokines combination may be a novel strategy for the treatment of HCC.