Cell membrane fluidity and adriamycin retention in a tumor progression model of AKR lymphoma.
Counteraction of drug resistance is a major challenge in cancer therapy, particularly in advanced stages. The main mechanism of multidrug resistance is related to an increased drug efflux. In the present study we examined the effect of modifying cell membrane lipid fluidity on uptake of adriamycin (ADR) in cells of AKR lymphoma malignancy variants. Modification of cell membrane fluidity, either by lecithin or by lecithin-cholesterol mixtures, induced in a high proportion of cells of all variants a higher capacity to accumulate ADR. The chemosensitizing effect, for lecithin in particular, was proportional to the degree of malignancy of the lymphoma variants. The increased ADR uptake was up to 1.4-fold in the variant of lowest malignancy and up to 5-fold in the one of highest aggressiveness. This tendency correlates with our previous studies and is of particular value since highly-malignant tumors are often drug resistant. The cholesterol-lecithin mixture, induced, however, in part of the variants the appearance of a small subpopulation with very low ADR permeability. Cell membrane rigidification is of value for exposing tumor cell cryptic antigens but may be deleterious when used in conjunction with chemotherapy.
Leibovici
J
J
Department of Pathology, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Klein
O
O
Wollman
Y
Y
Donin
N
N
Mahlin
T
T
Shinitzky
M
M
D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D002784:Cholesterol / Q000494:pharmacology; D004317:Doxorubicin / Q000378:metabolism* / Q000494:pharmacology; D004351:Drug Resistance; D005434:Flow Cytometry; D008081:Liposomes / Q000378:metabolism; D008223:Lymphoma / Q000378:metabolism* / Q000648:ultrastructure*; D008560:Membrane Fluidity / Q000187:drug effects; D051379:Mice; D008806:Mice, Inbred AKR; D010713:Phosphatidylcholines / Q000494:pharmacology
D008081:Liposomes; D010713:Phosphatidylcholines; D004317:Doxorubicin; D002784:Cholesterol