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 hyp erthermia, in sensitive and multidrug-resistant MCF-7 human tumour cel ls using clonogenic assays. In the resistant subline, TLED was found t o partly circumvent multidrug resistance (MDR). The reversal was compa rable to that obtained when verapamil was added to free doxorubicin. W hen hyperthermic treatment was applied, no difference in thermosensiti vity was found between sensitive and resistant cells. The combination of hyperthermia with free doxorubicin did not reverse MDR. Hyperthermi a and TLED yielded additive effects in the resistant cells while poten tiation was observed in the sensitive cells. These results confirmed t he usefulness of the liposome encapsulation of doxorubicin in reversin g MDR. The possibility of obtaining additive cytotoxicity using TLED c ombined with hyperthermia may represent an alternative way of intensif ication of doxorubicin cytotoxicity concomitant with the circumvention of MDR without using MDR reversing agents, which often generate limit ing toxic side-effects.