Synergistic Apoptotic Effect of Combination Treatment with Troglitazone and COX-2 Inhibitor in Glioma Cells

Kim, Kyung Ryoul; Park, Min Young; Park, Ho Sung; Jang, Kyu Yun; Moon, Woo Sung; Lee, Dong Geun; Kang, Myoung Jae

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.