Alpha-fetoprotein-mediated targeting--a new strategy to overcome multidrug resistance of tumour cells in vitro.
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 gene mdr1. 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.
Moskaleva EYu
Moscow Research Institute of Medical Ecology, Russia.
Posypanova
G A
GA
Shmyrev
I I
II
Rodina
A V
AV
Muizhnek
E L
EL
Severin
E S
ES
Katukov VYu
Luzhkov
Y M
YM
Severin
S E
SE
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers; D018432:Drug Resistance, Multiple / Q000235:genetics; D005260:Female; D019450:Genes, MDR; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology; D000509:alpha-Fetoproteins / Q000008:administration & dosage*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D000509:alpha-Fetoproteins; D004317:Doxorubicin; D014700:Verapamil