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

Author:

Arantes-Rodrigues Regina1,Pinto-Leite Rosário2,Fidalgo-Gonçalves Lio3,Palmeira Carlos45,Santos Lúcio45,Colaço Aura6,Oliveira Paula1

Affiliation:

1. Centre 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

2. Genetic Service, Cytogenetic Laboratory, Hospital Center of Trás-os-Montes and Alto Douro, 5000-508 Vila Real, Portugal

3. Department of Engineering, CMUTAD, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal

4. Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-072 Porto, Portugal

5. Health School, University Fernando Pessoa, 4249-004 Porto, Portugal

6. Department of Veterinary Sciences, CECAV, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal

Abstract

The aim of this paper is to analyse sunitinib malatein vitroability 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 (). 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 confirmedin vivo, this conjugation may provide a means of new perspectives in muscle-invasive urinary bladder cancer treatment.

Funder

Ministério da Educação e Ciência

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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