Objective： To study the effect of ciglitazone on hepatic cancer cells HepG2 growth in vitro and in vivo and its mechanisms. Methods： The in vitro cultured HepG2 lines were treated with various concentrations of cigl...Objective： To study the effect of ciglitazone on hepatic cancer cells HepG2 growth in vitro and in vivo and its mechanisms. Methods： The in vitro cultured HepG2 lines were treated with various concentrations of ciglitazone. The in vitro growth of HepG2 cells was examined by growth curve and the cell cycle was analyzed by flow cytometry. HepG2 cells （1×10^6 /mouse） were inoculated subcutaneously into 20 nude mice to establish the hepatocellular carcinoma model. The mice were randomly divided into two groups： the control group （group A, n=10） and the ciglitazone-treated group （group B, n=10）. The mice in the group B were injected with 100μL （100μmol/L） of ciglitazone every other day for 15 times, while the mice in the group A with saline instead. One month later, the weights of the resected subcutaneous tumors and suppression rates were measured. The expression of cyclinD1 and P21 was detected by Western blot. Results： The proliferation of HepG2 was significantly inhibited by ciglitazone in a dose- and timedependant manner. There were more cells arrested in G1/G0 phase and the expression of PPARγ was markedly up-regulated in HepG2 cells treated with ciglitazone. After the treatment with ciglitazone, the average weights of the tumors in the group A and B were 3.73±0.22 g and 2.60±0.35 g, respectively, and the tumor suppression rate in the group B was 30%. The expression of cyclinD1 was increased significantly, while that of P21 was decreased significantly in group A as compared with that in group B. Conclusion： Ciglitazone could significantly inhibit HepG2 proliferation in a dose- and time-dependent manner, and induce differentiation of HepG2, the mechanism of which may be related to the PPARγ intervention to cell cycle control.展开更多
Nonalcoholic fatty liver disease （NAFLD） is highly prevalent and can result in nonalcoholic steatohepatitis （NASH） and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of ...Nonalcoholic fatty liver disease （NAFLD） is highly prevalent and can result in nonalcoholic steatohepatitis （NASH） and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of literature implicates the peroxisome proliferators- activated receptors （PPARs） in the pathogenesis and treatment of NAFLD. These nuclear hormone receptors impact on hepatic triglyceride accumulation and insulin resistance. The aim of this review is to describe the data linking PPARα and PPART to NAFLD/NASH and to discuss the use of PPAR ligands for the treatment of NASH.展开更多
AIM: To evaluate the effect of rosiglitazone in a murine model of liver fibrosis induced by Schistosoma japonicum infection. METHODS: A total of 50 mice were randomly and averagely divided into groups A, B, C, D and E...AIM: To evaluate the effect of rosiglitazone in a murine model of liver fibrosis induced by Schistosoma japonicum infection. METHODS: A total of 50 mice were randomly and averagely divided into groups A, B, C, D and E. The mice in group A served as normal controls, while those in the other four groups were infected with Schistosoma japonicum to induce the model of liver fibrosis. Besides, the mice in groups C, D and E were treated with praziquantel, rosiglitazone and praziquantel plus rosiglitazone, respectively. NF-κB binding activity and expression of PPARγ-mRNA were determined by Western blot assay and real-time quantitative PCR. Radioimmunonassay technique was used to detect the serum content changes of TNF-α and IL-6. Histological specimens were stained with HE. Expression of TGF-β1, a-smooth muscle actin and type ?Ⅰ?and type Ⅲ collagen was detected by immunohistochemistry and multimedia color pathographic analysis system. RESULTS: Inflammation and fibrosis in the rosiglitazone plus praziquantel treatment group (group E) were lightest among the mice infected with Schistosoma (P < 0.05). To further explore the mechanism of rosiglitazone action, we found that rosiglitazone can significantly increase the expression of PPARγ [E: -18.212 ± (-3.909) vs B: -27.315 ± (-6.348) and C: -25.647 ± (-5.694), P < 0.05],reduce the NF-κB binding activity (E: 88.89 ± 19.34 vs B: 141.11 ± 15.37, C: 112.89 ± 20.17 and D: 108.89 ± 20.47, P < 0.05), and lower the serum level of TNF-α (E: 1.613 ± 0.420 ng/mL vs B: 2.892 ± 0.587 ng/mL, C: 2.346 ± 0.371 ng/mL and D: 2.160 ± 0.395 ng/mL, P < 0.05) and IL-6 (E: 0.106 ± 0.021 ng/mL vs B: 0.140 ± 0.031 ng/mL and C: 0.137 ± 0.027 ng/mL, P < 0.05) in mice with liver fibrosis. Rosiglitazone can also substantially reduce the hepatic expression of TGF-β1, α-SMA type Ⅰand type Ⅲ collagen in mice with liver fibrosis. CONCLUSION: The activation of PPARγ by its ligand can retard liver fibrosis and suggest the use of rosiglitazone for the treatment of liver fibrosis due to Schistosoma japonicum infection.展开更多
文摘Objective： To study the effect of ciglitazone on hepatic cancer cells HepG2 growth in vitro and in vivo and its mechanisms. Methods： The in vitro cultured HepG2 lines were treated with various concentrations of ciglitazone. The in vitro growth of HepG2 cells was examined by growth curve and the cell cycle was analyzed by flow cytometry. HepG2 cells （1×10^6 /mouse） were inoculated subcutaneously into 20 nude mice to establish the hepatocellular carcinoma model. The mice were randomly divided into two groups： the control group （group A, n=10） and the ciglitazone-treated group （group B, n=10）. The mice in the group B were injected with 100μL （100μmol/L） of ciglitazone every other day for 15 times, while the mice in the group A with saline instead. One month later, the weights of the resected subcutaneous tumors and suppression rates were measured. The expression of cyclinD1 and P21 was detected by Western blot. Results： The proliferation of HepG2 was significantly inhibited by ciglitazone in a dose- and timedependant manner. There were more cells arrested in G1/G0 phase and the expression of PPARγ was markedly up-regulated in HepG2 cells treated with ciglitazone. After the treatment with ciglitazone, the average weights of the tumors in the group A and B were 3.73±0.22 g and 2.60±0.35 g, respectively, and the tumor suppression rate in the group B was 30%. The expression of cyclinD1 was increased significantly, while that of P21 was decreased significantly in group A as compared with that in group B. Conclusion： Ciglitazone could significantly inhibit HepG2 proliferation in a dose- and time-dependent manner, and induce differentiation of HepG2, the mechanism of which may be related to the PPARγ intervention to cell cycle control.
文摘Nonalcoholic fatty liver disease （NAFLD） is highly prevalent and can result in nonalcoholic steatohepatitis （NASH） and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of literature implicates the peroxisome proliferators- activated receptors （PPARs） in the pathogenesis and treatment of NAFLD. These nuclear hormone receptors impact on hepatic triglyceride accumulation and insulin resistance. The aim of this review is to describe the data linking PPARα and PPART to NAFLD/NASH and to discuss the use of PPAR ligands for the treatment of NASH.
文摘AIM: To evaluate the effect of rosiglitazone in a murine model of liver fibrosis induced by Schistosoma japonicum infection. METHODS: A total of 50 mice were randomly and averagely divided into groups A, B, C, D and E. The mice in group A served as normal controls, while those in the other four groups were infected with Schistosoma japonicum to induce the model of liver fibrosis. Besides, the mice in groups C, D and E were treated with praziquantel, rosiglitazone and praziquantel plus rosiglitazone, respectively. NF-κB binding activity and expression of PPARγ-mRNA were determined by Western blot assay and real-time quantitative PCR. Radioimmunonassay technique was used to detect the serum content changes of TNF-α and IL-6. Histological specimens were stained with HE. Expression of TGF-β1, a-smooth muscle actin and type ?Ⅰ?and type Ⅲ collagen was detected by immunohistochemistry and multimedia color pathographic analysis system. RESULTS: Inflammation and fibrosis in the rosiglitazone plus praziquantel treatment group (group E) were lightest among the mice infected with Schistosoma (P < 0.05). To further explore the mechanism of rosiglitazone action, we found that rosiglitazone can significantly increase the expression of PPARγ [E: -18.212 ± (-3.909) vs B: -27.315 ± (-6.348) and C: -25.647 ± (-5.694), P < 0.05],reduce the NF-κB binding activity (E: 88.89 ± 19.34 vs B: 141.11 ± 15.37, C: 112.89 ± 20.17 and D: 108.89 ± 20.47, P < 0.05), and lower the serum level of TNF-α (E: 1.613 ± 0.420 ng/mL vs B: 2.892 ± 0.587 ng/mL, C: 2.346 ± 0.371 ng/mL and D: 2.160 ± 0.395 ng/mL, P < 0.05) and IL-6 (E: 0.106 ± 0.021 ng/mL vs B: 0.140 ± 0.031 ng/mL and C: 0.137 ± 0.027 ng/mL, P < 0.05) in mice with liver fibrosis. Rosiglitazone can also substantially reduce the hepatic expression of TGF-β1, α-SMA type Ⅰand type Ⅲ collagen in mice with liver fibrosis. CONCLUSION: The activation of PPARγ by its ligand can retard liver fibrosis and suggest the use of rosiglitazone for the treatment of liver fibrosis due to Schistosoma japonicum infection.
