PPARγ Ligand-Induced Decrease of in vivo Tumor Growth Accompanied by Increased Cytolytic Activity of Splenocytes
장규윤, 김경렬, 박호성, 문우성, 이동근, 강명재, 유기훈, 이학용, 최하나, 차은정,
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장규윤 ( Jang Kyu-Yun )
전북대학교 의과대학 병리학교실 및 의과학연구소
김경렬 ( Kim Kyung-Ryoul )
전북대학교 의과대학 병리학교실 및 의과학연구소
박호성 ( Park Ho-Sung )
전북대학교 의과대학 병리학교실 및 의과학연구소
문우성 ( Moon Woo-Sung )
전북대학교 의과대학 병리학교실 및 의과학연구소
이동근 ( Lee Dong-Geun )
전북대학교 의과대학 병리학교실 및 의과학연구소
강명재 ( Kang Myoung-Jae )
전북대학교 의과대학 병리학교실 및 의과학연구소
유기훈 ( Yu Ki-Hoon )
전북대학교 의과대학 병리학교실 및 의과학연구소
이학용 ( Lee Hak-Yong )
전북대학교 의과대학 병리학교실 및 의과학연구소
최하나 ( Choi Ha-Na )
전북대학교 의과대학 병리학교실 및 의과학연구소
차은정 ( Cha Eun-Jung )
전북대학교 의과대학 병리학교실 및 의과학연구소
KMID : 0357920070410010007
Abstract
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 20μM ROS caused an increase in the cytolytic activity of splenocytes, and a concentration of 50μM 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.
키워드
Peroxisome proliferators-activator receptors; Spleen; NK cells; Glioma; Neoplasms
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