Effect of mitoxantrone liposomes on multidrug-resistant breast cancer cells.
A major obstacle in efficacy of breast cancer chemotherapy is the emergence of multidrug resistance. We investigated modulation of multidrug resistance by liposome-encapsulated mitoxantrone in a drug resistant human breast MCF7R cell line and the influence of liposome composition. Neutral high phase-transition temperature and anionic low phase-transition temperature phospholipid liposomes, reduced the resistance factor from 142 to 15 and 38, respectively. The higher cytotoxicity obtained with mitoxantrone-encapsulation was not necessarily related to higher intracellular uptake. Our data suggest that liposomes, according to their lipid composition, may alter the P-glycoprotein function by plasma membrane stabilization and modulate multidrug resistance in human cancer.
Poujol
S
S
Department of Oncopharmacology, Cancer Institute C.R.L.C., Montpellier, France.
Tilleul
P
P
Astre
C
C
Martel
P
P
Fabbro
M
M
Pinguet
F
F
D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004337:Drug Carriers; D018432:Drug Resistance, Multiple; D006801:Humans; D007150:Immunohistochemistry; D008081:Liposomes; D008942:Mitoxantrone / Q000378:metabolism / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D008942:Mitoxantrone; D014700:Verapamil