Vincristine resistance development in lymphoblastoid cells under conditions of selective P-glycoprotein inhibition.
Most studies looking at the reversal of drug resistance in hematological malignancies have focused on the blockade of P-glycoprotein (Pgp) pump activity, as one of the more important proteins involved in cell resistance to the chemotherapeutic agents used. In model experiments using the IM-9 lymphoblastoid cell line cultured with increasing doses of vincristine (Vcr) in the presence or absence of the Pgp blocker cyclosporin A (CsA) we established two Vcr resistant sublines. By measuring Pgp expression in target cells, and the activity and sensitivity to cytostatics we believe that our results suggest the presence of other mechanisms involved in cell resistance to xenobiotics and that these mechanisms should be considered in the development of clinical trials designed to overcome drug resistance.
Svirnovski
Arcadi
A
Laboratory for Molecular Genetics Investigations in Leukemia and Blood Disorders, Republican Research and Practical Center for Hematology and Transfusiology, Ministry of Health, 160 Dolginovski Tract, Minsk 223-059, Belarus. svirnov@users.med.by
Pasiukov
Vadim
V
Grigorovich
Sergei
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D014750:Vincristine / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D014750:Vincristine; D016572:Cyclosporine