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An. acad. bras. ciênc ; 73(1): 57-69, Mar. 2001. ilus, graf
Article in English | LILACS | ID: lil-281085

ABSTRACT

Multidrug resistance to chemotherapy is a major obstacle in the treatment of cancer patients. The best characterised mechanism responsible for multidrug resistance involves the expression of the MDR-1 gene product, P-glycoprotein. However, the resistance process is multifactorial. Studies of multidrug resistance mechanisms have relied on the analysis of cancer cell lines that have been selected and present cross-reactivity to a broad range of anticancer agents. This work characterises a multidrug resistant cell line, originally selected for resistance to the Vinca alkaloid vincristine and derived from the human erythroleukaemia cell K562. This cell line, named Lucena 1, overexpresses P-glycoprotein and have its resistance reversed by the chemosensitisers verapamil, trifluoperazine and cyclosporins A, D and G. Furthermore, we demonstrated that methylene blue was capable of partially reversing the resistance in this cell line. On the contrary, the use of 5-fluorouracil increased the resistance of Lucena 1. In addition to chemotherapics, Lucena 1 cells were resistant to ultraviolet A radiation and hydrogen peroxide and failed to mobilise intracellular calcium when thapsigargin was used. Changes in the cytoskeleton of this cell line were also observed


Subject(s)
Humans , Antineoplastic Agents, Phytogenic/pharmacology , Drug Resistance, Multiple , K562 Cells/drug effects , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Vincristine/pharmacology , Drug Resistance, Multiple/genetics , Gene Expression , Leukemia, Erythroblastic, Acute/drug therapy , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Phenotype
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