Physiological and molecular effects of Apo2L/TRAIL and cisplatin in ovarian carcinoma cell lines

被引:43
作者
Siervo-Sassi, RR [1 ]
Marrangoni, AM [1 ]
Feng, X [1 ]
Naoumova, N [1 ]
Winans, M [1 ]
Edwards, RP [1 ]
Lokshin, A [1 ]
机构
[1] Univ Pittsburgh, Magee Womens Res Inst, Dept Ob Gyn Reprod Sci, Pittsburgh, PA 15213 USA
关键词
ovarian cancer; cisplatin; Apo2L/TRAIL; apoptosis;
D O I
10.1016/S0304-3835(02)00579-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Combining of tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) with a chemotherapeutic drug, cisplatin, in ovarian carcinoma cell lines exerted potent anti-tumor effects that exceeded the effects of each drug alone. In order to investigate mechanisms of anti-tumor activity of cisplatin/Apo2L/TRAIL combination, we assessed in detail the molecular effects of cisplatin and Apo2L/TRAIL-activated cell death in two ovarian carcinoma cell lines, OVCAR3 and SKOV3, using cDNA array hybridization, Western blot and flow cytometry. We observed differential induction of apoptosis-related molecules by cisplatin and Apo2L/TRAIL. Cisplatin upregulated the expression of both death and decoy TRAIL receptors, as well as of TRAF5 and -6, downregulated the anti-apoptotic proteins, Bcl-2, and induced activation of caspases-3, -8 and -9. Apo2L/TRAIL induced the expression of pro-apoptotic proteins, Bad and Bax; downregulated the anti-apoptotic proteins, Bcl-2 and Bcl-xL; and activated caspases-3, -7, -8, -9 and -10. Cisplatin/Apo2L/TRAIL combination resulted in further downregulation of expression of antiapoptotic proteins, Bcl-2 and Bcl-xL, as well as an increase in mitochondrial permeability transition and activation of caspases-3,-8, and -10. These data demonstrate positive cooperation of cisplatin and Apo2L/TRAIL and emphasize the potential clinical usefulness of cisplatin/Apo2L/TRAIL combination therapy. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:61 / 72
页数:12
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