KMID : 0357920070410010007
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Korean Journal of Pathology 2007 Volume.41 No. 1 p.7 ~ p.14
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PPAR¥ã Ligand-Induced Decrease of in vivo Tumor Growth Accompanied by Increased Cytolytic Activity of Splenocytes
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Jang Kyu-Yun
Kim Kyung-Ryoul Park Ho-Sung Moon Woo-Sung Lee Dong-Geun Kang Myoung-Jae Yu Ki-Hoon Lee Hak-Yong Choi Ha-Na Cha Eun-Jung
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Abstract
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Background : Recent studies have proposed the use of peroxisome proliferator activated receptor-¥ã (PPAR¥ã) ligands as new chemotherapeutic agents for human malignant tumors. However the in vivo mechanism of PPAR¥ã ligands on cellular toxicity is not clear. Therefore we examined the anti-tumor effects of the PPAR¥ã 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¥ìM ROS caused an increase in the cytolytic activity of splenocytes, and a concentration of 50¥ìM 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 PPAR¥ã ligands in vivo. However, the roles of NK cells in the PPAR¥ã ligand-induced anti-tumor activity should be further investigated.
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KEYWORD
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Peroxisome proliferators-activator receptors, Spleen, NK cells, Glioma, Neoplasms
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