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BioMed Research International
Volume 2013 (2013), Article ID 791406, 11 pages
Research Article

Synergistic Effect between Cisplatin and Sunitinib Malate on Human Urinary Bladder-Cancer Cell Lines

1Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro, Vila Real, 5001-801 Vila Real, Portugal
2Genetic Service, Cytogenetic Laboratory, Hospital Center of Trás-os-Montes and Alto Douro, 5000-508 Vila Real, Portugal
3Department of Engineering, CMUTAD, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal
4Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-072 Porto, Portugal
5Health School, University Fernando Pessoa, 4249-004 Porto, Portugal
6Department of Veterinary Sciences, CECAV, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal

Received 13 May 2013; Accepted 31 October 2013

Academic Editor: Joohun Ha

Copyright © 2013 Regina Arantes-Rodrigues et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The aim of this paper is to analyse sunitinib malate in vitro ability to enhance cisplatin cytotoxicity in T24, 5637, and HT1376 human urinary bladder-cancer cell lines. Cells were treated with cisplatin (3, 6, 13, and 18 μM) and sunitinib malate (1, 2, 4, 6, and 20 μM), either in isolation or combined, over the course of 72 hours. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, acridine orange, and monodansylcadaverine staining and flow cytometry were performed. The combination index (CI) was calculated based on the Chou and Talalay method. In isolation, cisplatin and sunitinib malate statistically ( ) decrease cell viability in all cell lines in a dose-dependent manner, with the presence of autophagic vacuoles. A cell cycle arrest in early S-phase and in G0/G1-phase was also found after exposure to cisplatin and sunitinib malate, in isolation, respectively. Treatment of urinary bladder-cancer cells with a combination of cisplatin and sunitinib malate showed a synergistic effect ( ). Autophagy and apoptosis studies showed a greater incidence when the combined treatment was put into use. This hints at the possibility of a new combined therapeutic approach. If confirmed in vivo, this conjugation may provide a means of new perspectives in muscle-invasive urinary bladder cancer treatment.