J Appl Biomed 11:79-92, 2013 | DOI: 10.2478/v10136-012-0034-7

Meloxicam synergistically enhances the in vitro effects of sunitinib malate on bladder-cancer cells

Regina Arantes-Rodrigues¹, Rosário Pinto-Leite², Lio Fidalgo-Gonçalves³, Isabel Gaivão⁴, Aura Colaço¹, Paula Oliveira^1,*, Lúcio Santos⁵

¹ Department of Veterinary Sciences, CECAV, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal

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

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

⁴ Department of Genetics and Biotechnology, CECAV, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal

⁵ Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, Porto, Portugal

To evaluate the in vitro effects of sunitinib malate and meloxicam in isolation, and to analyse the ability of meloxicam to enhance the cytotoxicity of sunitinib malate in three human bladder-cancer cell lines. Cell lines were treated with sunitinib malate and meloxicam, either in isolation or combined. Leishman staining, MTT method, comet assay, MDC staining and M30 CytoDEATH antibody were performed. The Chou and Talalay method was applied. Sunitinib malate and meloxicam supressed cell proliferation in bladder-cancer cells in isolation, in a concentration-dependent manner. Treatment of bladder-cancer cells with a combination of sunitinib malate and meloxicam showed a synergistic effect. When exploring the mechanism of this combination by means of comet assay, there is the suggestion that meloxicam increases sunitinib malate cytotoxicity through DNA damage. Autophagic and apoptotic studies show a greater incidence of autophagic vacuoles and early apoptotic cells when the combined treatment was put into use. In isolation, sunitinib malate and meloxicam demonstrated anti-tumour effects in our study. Furthermore, simultaneous exposure of cells to sunitinib malate and meloxicam provided a combinatorial beneficial effect. This hints at the possibility of a new combined therapeutic regimen, which could lead to improvements in the treatment of patients with bladder cancer.

Keywords: bladder cancer; bladder-cancer cell lines; sunitinib malate; meloxicam; synergistic

Received: December 31, 2012; Revised: January 2, 2013; Published: July 31, 2013  Show citation