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Background : Recent studies have proposed the use of peroxisome proliferator activated receptor-γ (PPARγ) ligands as new chemotherapeutic agents for human malignant tumors. However the in vivo mechanism of PPARγ ligands on cellular toxicity is not clear. Therefore we examined the anti-tumor effects of the PPARγ ligand, rosiglitazone (ROS), in animal models. Methods : To evaluate the effect of RSO on splenocytes, an in vitro and in vivo study was performed. Cytolytic activity was measured by use of a 51Cr release assay. The splenic natural killer (NK) cell population and effector-target conjugation were measured by flow cytometric analysis. Results : In 9L glioma bearing rats, 30 mg/kg/d of ROS treatment induced a significant decrease of subcutaneous tumor growth accompanied by an increased cytolytic activity of splenocytes and of the splenic NKR-P1bright/CD3- NK cell population. In normal rats, systemic administration of ROS also increased the cytolytic activity of splenocytes, the splenic NK cell population, and effector-target conjugation. Moreover, we found that a concentration of 20 μM ROS caused an increase in the cytolytic activity of splenocytes, and a concentration of 50 μM ROS increased effector-target conjugation in vitro. Conclusion : These results suggest that increased splenic cytolytic activity and NK cell population may contribute to the anti-tumor effects of PPARγ ligands in vivo. However, the roles of NK cells in the PPARγ ligand- induced anti-tumor activity should be further investigated.
Background : Recent studies have proposed the use of peroxisome proliferator activated receptor-γ (PPARγ) ligands as new chemotherapeutic agents for human malignant tumors. However the in vivo mechanism of PPARγ ligands on cellular toxicity is not clear. Therefore we examined the anti-tumor effects of the PPARγ ligand, rosiglitazone (ROS), in animal models. Methods : To evaluate the effect of RSO on splenocytes, an in vitro and in vivo study was performed. Cytolytic activity was measured by use of a 51Cr release assay. The splenic natural killer (NK) cell population and effector-target conjugation were measured by flow cytometric analysis. Results : In 9L glioma bearing rats, 30 mg/kg/d of ROS treatment induced a significant decrease of subcutaneous tumor growth accompanied by an increased cytolytic activity of splenocytes and of the splenic NKR-P1bright/CD3- NK cell population. In normal rats, systemic administration of ROS also increased the cytolytic activity of splenocytes, the splenic NK cell population, and effector-target conjugation. Moreover, we found that a concentration of 20 μM ROS caused an increase in the cytolytic activity of splenocytes, and a concentration of 50 μM ROS increased effector-target conjugation in vitro. Conclusion : These results suggest that increased splenic cytolytic activity and NK cell population may contribute to the anti-tumor effects of PPARγ ligands in vivo. However, the roles of NK cells in the PPARγ ligand- induced anti-tumor activity should be further investigated.
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Peroxisome proliferators-activator receptors; Spleen; NK cells; Glioma; Neoplasms
