title: Synergistic effect between cisplatin and sunitinib malate on human urinary bladder-cancer cell lines.
abstract: 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 (P < 0.05) 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 (CI < 1). 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.
authors.affiliation: 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.
authors.forename: Regina
authors.initials: R
authors.lastname: Arantes-Rodrigues
authors.affiliation: Genetic Service, Cytogenetic Laboratory, Hospital Center of Trás-os-Montes and Alto Douro, 5000-508 Vila Real, Portugal.
authors.forename: Rosário
authors.initials: R
authors.lastname: Pinto-Leite
authors.affiliation: Department of Engineering, CMUTAD, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal.
authors.forename: Lio
authors.initials: L
authors.lastname: Fidalgo-Gonçalves
authors.affiliation: Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-072 Porto, Portugal ; Health School, University Fernando Pessoa, 4249-004 Porto, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Palmeira
authors.affiliation: Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-072 Porto, Portugal ; Health School, University Fernando Pessoa, 4249-004 Porto, Portugal.
authors.forename: Lúcio
authors.initials: L
authors.lastname: Santos
authors.affiliation: Department of Veterinary Sciences, CECAV, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal.
authors.forename: Aura
authors.initials: A
authors.lastname: Colaço
authors.affiliation: 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.
authors.forename: Paula
authors.initials: P
authors.lastname: Oliveira
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D004357:Drug Synergism; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D000077210:Sunitinib; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D007211:Indoles; D011758:Pyrroles; D002945:Cisplatin; D000077210:Sunitinib