Avaliação "in vivo" e "in vitro" da resistencia a multiplas drogas

AUTOR(ES)
DATA DE PUBLICAÇÃO

1994

RESUMO

Multidrug resistance has been one of the most active research areas during last decade because its growing clinical importance. Expression of the MDR1 (170-Pglycoprotein) gene is an active effux pump that decreases the intracellular accumulation of some of the major anticancer drugs such as anthracyclines, vinca alkaloids, and epipodophyllotoxins. Our study stablished an "in vivo" model using BRO cell line and its transfected subline BROmdr1.1. The MDR phenotype was detected until the second passage as xenografts or 6 weeks in cell culture by citotoxity MTT test with vincristine and doxorubicin but also by imunostainning using 3 monoclonal antibodies (C219, JSBI and MRK16). We have studied antitumor activity of vincristine and doxorubicin in nude mice bearing the second passage of BRO and BROmdr1.1. It was possible to define resistant factors for each drug. New reversal agents, cremophor and bepridil, were tested "in vitro". Bepridil presented higher reversal effect and was select to "in vivo" studies, but the doses nedded to achieved complete reversal "in vitro" could not be reached "in vivo". BROmdr1.1 xenografts were treated with monoclonal antibodies labelled with isotopes. The absence of response probably was because it was not possible to concentrate de isotope in the resistant tumors due the small number of epitopes that this cell line presented at Scatchard test. This model can be used to study new reversal agents for MDR phenotype "in vivo", Its toxicity, pharmacokinetics and reversal activity, before going further on human trials

ASSUNTO(S)

agentes antineoplasicos cancer - quimioterapia imunoterapia drogas

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