A avances in Brief Increased Accumulation of Drugs in Multidrug-resistant Cells Induced by Liposomes 1

A multidrug-resistant cell such as the human lymphoblastic leukemic cell CEM/VLBioo accumulates far less vinblastine (VLB) than its drugsensitive parent, CEM. When CEM/VLB)0o cells are exposed to lipo somes consisting of the phospholipids cardiolipin, dioleoylphosphatidic acid, or phosphatidylinositol bearing unsaturated fatty acids and then tested for uptake of VLB, accumulation of drug rapidly rises to levels approaching those of CEM cells, which are relatively unaffected by the liposome treatment. The liposomes are not carriers of entrapped drug. Phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine are inactive, and the addition of cholesterol to liposomes inhibits uptake. Exposure of cells to liposomes does not appear to alter the efflux of drugs. We suggest that the liposomal lipids, introduced into the plasma membranes of CEM/VLBIOOcells, change their properties so that accu mulation of drugs by cells is largely restored. The cytotoxicity of VLB in CEM/VLBIOo cells is increased approximately 10-fold by cardiolipin

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