Multidrug resistance in tumour cells: characterisation of the multidrug resistant cell line K562-Lucena 1

Multidrug resistance to chemotherapy is a major obstacle in the treatment o f cancer patients. The best characterised mechanism responsible for multidr ug resistance involves the expression of the MDR-1 gene product, P-glycopro tein. However, the resistance process is multifactorial. Studies of multidr ug resistance mechanisms have relied on the analysis of cancer cell lines t hat have been selected and present cross-reactivity to a broad range of ant icancer agents. This work characterises a multidrug resistant cell line, or iginally selected for resistance to the Vinca alkaloid vincristine and deri ved from the human erythroleukaemia cell K562. This cell line, named Lucena 1, overexpresses P-glycoprotein and have its resistance reversed by the ch emosensitisers verapamil, trifluoperazine and cyclosporins A, D and G. Furt hermore, we demonstrated that methylene blue was capable of partially rever sing the resistance in this cell line. On the contrary, the use of 5-fluoro uracil increased the resistance of Lucena 1. In addition to chemotherapies, Lucena 1 cells were resistant to ultraviolet A radiation and hydrogen pero xide and failed to mobilise intracellular calcium when thapsigargin was use d. Changes in the cytoskeleton of this cell line were also observed.