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ALPHA-FETOPROTEIN-MEDIATED TARGETING—A NEW STRATEGY TO OVERCOME MULTIDRUG RESISTANCE OF TUMOUR CELLSIN VITRO
Authors:ELIZAVETA YU. MOSKALEVA  GALINA A. POSYPANOVA  IGOR I. SHMYREV  ALLA V. RODINA  EKATERINA L. MUIZHNEK  EUGENE S. SEVERIN  VALERY YU. KATUKOV  YURY M. LUZHKOV  SERGEI E. SEVERIN
Affiliation:aMoscow Research Institute of Medical Ecology, Sympheropolsky blvd.8, Moscow, 113149, Russia
Abstract:The possibility of overcoming the multidrug resistance of human malignant cells by using doxorubicin conjugated to alpha-fetoprotein (AFP) was studied. It was shown that this type of antitumour drugs, penetrating the cell by receptor-mediated endocytosis with AFP as a vehicle, raises the sensitivity of the tumour cells that are resistant due to the expression of the multidrug resistance genemdr1. The sensitivity of antibiotic-resistant cell lines SKVLB (a human ovarian carcinoma) and MCF-7 AdrR (a human breast carcinoma) increased by 10- and 4-fold, respectively, when AFP-conjugated doxorubicin was used. The rationale of using human AFP-antitumour drug conjugates for the development of new chemotherapeutic approaches to cancer treatment is discussed.
Keywords:AFP   AFP-conjugates with drugs (doxorubicin)   targeted delivery   multidrug resistance   P-glycoprotein   tumour cells
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