Effect of liposomes on P-glycoprotein function in multidrug resistant cells.
Presentation of doxorubicin in liposomes has shown to enhance the sensitivity of multidrug resistant CH LZ cells to the drug (Thierry et al. Cancer Commun. 1:311-316, 1989). We confirmed that liposomally encapsulated doxorubicin may partially overcome multidrug resistance in the human ovarian carcinoma SKVLB cell line and that this effect is, at least in part, due to an increase of cellular drug accumulation. When used at high concentration, empty liposomes appear to be specifically cytotoxic in the MDR SKVLB and CH LZ cells. As observed with certain multidrug resistance modulators, empty liposomes inhibited the specific [3H]-vincristine binding to P-glycoprotein-enriched membranes isolated from CH LZ cells (60% at 0.2 mg lipid/ml). Our data suggest that liposomes may alter the P-glycoprotein function by direct interaction.
Thierry
A R
AR
Department of Radiation Medicine, Vincent T. Lombardi Cancer Center, Georgetown University Medical Center, Washington, D.C. 20007.
Dritschilo
A
A
Rahman
A
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004337:Drug Carriers; D008081:Liposomes; D008562:Membrane Glycoproteins; D014750:Vincristine; D004317:Doxorubicin