Troglitazone과 COX-2 억제제 병합 투여가 아교모세포종 세포의 세포자멸사에 미치는 영향
Synergistic Apoptotic Effect of Combination Treatment with Troglitazone and COX-2 Inhibitor in Glioma Cells
김경렬, 박민영, 박호성, 장규윤, 문우성, 이동근, 강명재,
소속 상세정보
김경렬 ( Kim Kyung-Ryoul )
전북대학교 의과대학 병리학교실 및 의과학연구소
박민영 ( Park Min-Young )
전북대학교 의과대학 병리학교실 및 의과학연구소
박호성 ( Park Ho-Sung )
전북대학교 의과대학 병리학교실 및 의과학연구소
장규윤 ( Jang Kyu-Yun )
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
KMID : 0357920070410010001
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 (5μM) and COX-2 inhibitor (5μM) 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.
키워드
Troglitazone; Cyclooxygenase-2; Glioma; Apoptosis
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