Antiproliferative activity of thermosensitive liposome-encapsulated doxorubicin combined with 43 degrees C hyperthermia in sensitive and multidrug-resistant MCF-7 cells.
Thermosensitive liposome-encapsulated doxorubicin (TLED) was compared to free doxorubicin, at 37 degrees C or combined with 43 degrees C hyperthermia, in sensitive and multidrug-resistant MCF-7 human tumour cells using clonogenic assays. In the resistant subline, TLED was found to partly circumvent multidrug resistance (MDR). The reversal was comparable to that obtained when verapamil was added to free doxorubicin. When hyperthermic treatment was applied, no difference in thermosensitivity was found between sensitive and resistant cells. The combination of hyperthermia with free doxorubicin did not reverse MDR. Hyperthermia and TLED yielded additive effects in the resistant cells while potentiation was observed in the sensitive cells. These results confirmed the usefulness of the liposome encapsulation of doxorubicin in reversing MDR. The possibility of obtaining additive cytotoxicity using TLED combined with hyperthermia may represent an alternative way of intensification of doxorubicin cytotoxicity concomitant with the circumvention of MDR without using MDR reversing agents, which often generate limiting toxic side-effects.
Merlin
J L
JL
Centre Alexis Vautrin, Laboratoire de Recherche, Vandoeuvre-Les-Nancy, France.
Marchal
S
S
Ramacci
C
C
Notter
D
D
Vigneron
C
C
D000230:Adenocarcinoma / Q000628:therapy; D001943:Breast Neoplasms / Q000628:therapy; D002455:Cell Division / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D008081:Liposomes; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D008081:Liposomes; D004317:Doxorubicin