Synergistic Apoptotic Effect of Combination Treatment with Troglitazone and COX-2 Inhibitor in Glioma Cells.
- Author:
Kyung Ryoul KIM
;
Min Young PARK
;
Ho Sung PARK
;
Kyu Yun JANG
;
Woo Sung MOON
;
Dong Geun LEE
;
Myoung Jae KANG
- Publication Type:Original Article
- Keywords:
Troglitazone;
Cyclooxygenase-2;
Glioma;
Apoptosis
- MeSH:
Apoptosis;
bcl-2-Associated X Protein;
Blotting, Western;
Cyclooxygenase 2;
DNA Fragmentation;
Down-Regulation;
Glioma*;
PPAR gamma;
Trypan Blue
- From:Korean Journal of Pathology
2007;41(1):1-6
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: The use of troglitazone (a PPARgamma ligand) and COX-2 inhibitor have been intensively studied for inhibition of tumor growth in cancer treatment, but the anti-tumor effect with a combination of these agents for cancer has not yet been studied. The aim of this study was to determine if low concentrations of troglitazone with COX-2 inhibitor in combination would cause significant cytotoxicity in glioma cells. METHODS: The effects of co-treatment with troglitazone and COX-2 inhibitor on cell growth and apoptosis were assessed by use of trypan blue exclusion and a DNA fragmentation assay. A western blot was used to analyze the apoptotic signaling for the expression of bcl-2, bax, PARP and p21 proteins. RESULTS: A low dose of troglitazone (5micrometer) and COX-2 inhibitor (5micrometer) strongly enhanced the cell growth inhibition and apoptosis in glioma cells when compared to a low dose of each drug alone. Western blotting analysis showed a decreased expression of bcl-2 and PARP proteins. In contrast, the bax protein level was increased. CONCLUSIONS: The combination of troglitazone and COX-2 inhibitor in a low dose elicits synergistic cytotoxicity in glioma cells. Our study also demonstrates that down regulation of bcl-2, fragmentation of PARP protein and increased expression of bax protein were accompanied by co-treatment with troglitazone and the COX-2 inhibitor.
