Multidrug resistance in tumour cells: characterization of the multidrug resistant cell line K562-Lucena 1.
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.
Departamento de Bioquímica Médica, Instituto de Ciências Biomédicas, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. vivian@bioqmed.ufrj.br
V M
VM
Rumjanek
G S
GS
Trindade
K
K
Wagner-Souza
M C
MC
de-Oliveira
L F
LF
Marques-Santos
R C
RC
Maia
M A
MA
Capella
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D020014:K562 Cells / Q000187:drug effects*; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy; D010641:Phenotype; D014750:Vincristine / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine