PPARgamma Ligand-Induced Decrease of in vivo Tumor Growth Accompanied by Increased Cytolytic Activity of Splenocytes.
- Author:
Kyu Yun JANG
1
;
Ki Hoon YU
;
Hak Yong LEE
;
Kyung Ryoul KIM
;
Ha Na CHOI
;
Eun Jung CHA
;
Ho Sung PARK
;
Woo Sung MOON
;
Myoung Jae KANG
;
Dong Geun LEE
Author Information
1. Department of Pathology, Chonbuk National University Medical School, Institute for Medical Sciences and Center for Healthcare Technology Development, Jeonju 561-180, Korea. kyjang@chonbuk.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Peroxisome proliferators-activator receptors;
Spleen;
NK cells;
Glioma;
Neoplasms
- MeSH:
Animals;
Glioma;
Humans;
Killer Cells, Natural;
Ligands;
Models, Animal;
Peroxisomes;
PPAR gamma*;
Rats;
Spleen
- From:Korean Journal of Pathology
2007;41(1):7-14
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Recent studies have proposed the use of peroxisome proliferator activated receptor-gamma (PPARgamma) ligands as new chemotherapeutic agents for human malignant tumors. However the in vivo mechanism of PPARgamma ligands on cellular toxicity is not clear. Therefore we examined the anti-tumor effects of the PPARgamma 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 20micrometer ROS caused an increase in the cytolytic activity of splenocytes, and a concentration of 50micrometer ROS increased effector-target conjugation in vitro. CONCLUSIONS: These results suggest that increased splenic cytolytic activity and NK cell population may contribute to the anti-tumor effects of PPARgamma ligands in vivo. However, the roles of NK cells in the PPARgamma ligand-induced anti-tumor activity should be further investigated.