AIM:To study the possible actions and mechanisms of peroxisome proliferator-activated receptorγ(PPARγ) ,a ligand-activated transcription factor,in pancreatic carcinogenesis,especially in angiogenesis. METHODS:Expressions of PPARγand retinoid acid receptor(RXRα) were examined by reverse-transcription polymerase chain reaction(RT-PCR) with immunocytochemical staining.Pancreatic carcinoma cells,PANC-1,were treated either with 9-cis-RA,a ligand of RXRα,or with 15-deoxy-Δ 12,14 prostaglandin J2(15d-PGJ2) ,a ligand of PPARγ,or both.Antiproliferative effect was evaluated by cell viability using methyltetrazolium(MTT) assay.A pancreatic carcinoma xenograft tumor model of nude mice was established by inoculating PANC-1 cells subcutaneously.Rosiglitazone,a specific ligand of PPARγ,was administered via water drinking in experimental group of nude mice.After 75 d,all mice were sacrificed.Expression of proliferating cell nuclear antigen(PCNA) in tumor tissue was examined with immunohistochemical staining.Expression of vascular endothelial growth factor(VEGF) mRNA in PANC-1 cells,which were treated with 15d-PGJ2 or 9-cis-RA at various concentrations or different duration,was detected by semi-quantitative RT-PCR.Effects of Rosiglitazone on changes of microvascular density(MVD) and VEGF expression were investigated in xenograft tumor tissue.Neovasculature was detected with immunohistochemistry staining labeled with anti-Ⅳcollagen antibody,and indicated by MVD. RESULTS:RT-PCR and immunocytochemical staining showed that PPARγand RXRαwere expressed in PANC-1 cells at both transcription level and translation level.MTT assay demonstrated that 15d-PGJ2,9-cis-RA and their combination inhibited the growth of PANC-1 cells in a dose-dependent manner.9-cis-RA had a combined inhibiting action with 15d-PGJ2 on the growth of pancreatic carcinoma.In vivo studies revealed that Rosiglitazone significantly suppressed the growth of pancreatic carcinoma as compared to control group(0.48±0.23 cm 3 vs 2.488±0.59 cm3,P<0.05) ,and the growth inhibition rate was 80.7%.Immunohistochemistry study showed that PCNA was down regulated in Rosiglitazone-treated group compared to the control group.15d-PGJ2,9-cis-RA and their combination inhibited the expression of VEGF mRNA in PANC-1 cells in a dose-and time-dependent manner. MVD was decreased more significantly in Rosiglitazonetreated mice(10.67±3.07) than in the control group(31.44±6.06)(P<0.01) .VEGF expression in xenograft tumor tissue was also markedly down-regulated in Rosiglitazone-treated mice. CONCLUSION:Activation of PPARγinhibits the growth of pancreatic carcinoma both in vitro and in vivo.Suppression of tumor angiogenesis by down-regulating the expression of VEGF may be one of the mechanisms by which PPARγactivation inhibits the growth of pancreatic carcinoma. AIM: To study the possible actions and mechanisms of peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activated transcription factor, in pancreatic carcinogenesis, especially in angiogenesis. METHODS: Expressions of PPARγ and retinoid acid receptor (RXRα) were examined by reverse- transcription polymerase chain reaction (RT-PCR) with immunocytochemical staining. Pancreatic carcinoma cells, PANC-1, were treated either with 9-cis-RA, a ligand of RXRα, or with 15-deoxy- Δ 12,14 prostaglandin J2 -PGJ2), a ligand of PPARγ, or both. Antiproliferative effect was evaluated by cell viability using methyltetrazolium (MTT) assay. A pancreatic carcinoma xenograft tumor model of nude mice was established by inoculating PANC-1 cells subcutaneously. Rosiglitazone, a specific ligand of PPARγ, was administered via water drinking in experimental group of nude mice. After 75 days, all mice were sacrificed. Expression of proliferating cell nuclear antigen (PCNA) in tumor tissue was examined with immunohistoche Expression of vascular endothelial growth factor (VEGF) mRNA in PANC-1 cells, which were treated with 15d-PGJ2 or 9-cis-RA at various concentrations or different duration, was detected by semi-quantitative RT-PCR. Effects of Rosiglitazone on changes of microvascular density (MVD) and VEGF expression were investigated in xenograft tumor tissue. Neovasculature was detected with immunohistochemistry staining labeled with anti-IV coli antibody, and indicated by MVD. RESULTS: RT-PCR and immunocytochemical staining showed that PPARγand RXRαwere expressed in PANC-1 cells at both transcription level and translation level. MTT assay of that 15d-PGJ2,9-cis-RA and their combination inhibited the growth of PANC-1 cells in a dose-dependent manner.9- cis-RA had a combined inhibiting action with 15d-PGJ2 on the growth of pancreatic carcinoma. vivo studies that that significantly inhibit the growth of pancreatic carcinoma as compared to control group (0.48 ± 0 .23 cm 3 vs 2.488 ± 0.59 cm3, P <0.05), and the growth inhibition rate was 80.7%. Immunohistochemistry study showed that PCNA was down regulated in Rosiglitazone-treated group compared to the control group 15d-PGJ2, 9-cis-RA and their (10.67 ± 3.07) than in the control group (31.44 ± 6.06) (P <0.01). The combination of the expression of VEGF mRNA in PANC-1 cells in a dose- and time-dependent manner. MVD was decreased more significantly in Rosiglitazonetreated mice . VEGF expression in xenograft tumor tissue was also markedly down-regulated in Rosiglitazone-treated mice. CONCLUSION: Activation of PPARγ inhibitors of the growth of pancreatic carcinoma both in vitro and in vivo. Inhibition of tumor angiogenesis by down-regulating the expression of VEGF may be one of the mechanisms by which PPARγactivation inhibits the growth of pancreatic carcinoma.