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Troglitazone과 COX-2 억제제 병합 투여가 아교모세포종세포의 세포자멸사에 미치는 영향

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

박민영|이동근|박호성|문우성|장규윤|강명재|김경열
대한병리학회|2007.02|Journal of Pathology and Translational Medicine|제41권 제1호|pp. 1-6

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참고문헌

주제분류병리학

초록

Abstract

Background : The use of troglitazone (a PPARγ 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 (5 μM) and COX-2 inhibitor (5 μM) 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.

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