CELL-MEMBRANE FLUIDITY AND ADRIAMYCIN RETENTION IN A TUMOR PROGRESSION MODEL OF AKR LYMPHOMA

Counteraction of drug resistance is a major challenge in cancer therap y, particularly in advanced stages. The main mechanism of multidrug re sistance is related to an increased drug efflux. In the present study we examined the effect of modifying cell membrane lipid fluidity on up take of adriamycin (ADR) in cells of AKR lymphoma malignancy variants. Modification of cell membrane fluidity, either by lecithin or by leci thin-cholesterol mixtures, induced in a high proportion of cells of al l variants a higher capacity to accumulate ADR. The chemosensitizing e ffect, for lecithin in particular, was proportional to the degree of m alignancy 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 previ ous studies and is of particular value since highly-malignant tumors a re often drug resistant. The cholesterol-lecithin mixture, induced, ho wever, in part of the variants the appearance of a small subpopulation with very low ADR permeability. Cell membrane rigidification is of va lue for exposing tumor cell cryptic antigens but may be deleterious wh en used in conjunction with chemotherapy.