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  • Title: Physiological and molecular effects of Apo2L/TRAIL and cisplatin in ovarian carcinoma cell lines.
    Author: Siervo-Sassi RR, Marrangoni AM, Feng X, Naoumova N, Winans M, Edwards RP, Lokshin A.
    Journal: Cancer Lett; 2003 Feb 10; 190(1):61-72. PubMed ID: 12536078.
    Abstract:
    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 anti-apoptotic 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.
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