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

Abstract

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.