Modulation of daunorubicin intracellular accumulation in P-glycoprotein expressing MCF-7 human breast adenocarcinoma cells by thermosensitive-liposome encapsulation and hyperthermia

• Published in: International journal of hyperthermia Vol. 11; no. 6; p. 855
• Main Authors: Merlin, J L, Marchal, S, Ramacci, C, Notter, D, Vigneron, C
• Format: Journal Article
• Language: English
• Published: England 1995
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - therapy; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - therapy; Coloring Agents; Combined Modality Therapy; Daunorubicin - administration & dosage; Daunorubicin - pharmacokinetics; Drug Carriers; Drug Resistance, Multiple; Female; Flow Cytometry; Fluorescence; Humans; Hyperthermia, Induced; Liposomes; Propidium; Tumor Cells, Cultured
• ISSN: 0265-6736
• DOI: 10.3109/02656739509052341

Intracellular accumulation of free or thermosensitive liposome-encapsulated daunorubicin (TLED) at 37 or 43 degrees C, was evaluated using flow cytometry in chemosensitive and P-glycoprotein expressing MCF-7 human breast adenocarcinoma cells. At 37 degrees C, liposome-encapsulation significantly increased intracellular daunorubicin accumulation (IDA) in resistant cells (P=0.005) and that effect was statistically comparable to that achieved in adding 15 micromol/l verapamil to free daunorubicin (DNR). Combining TLED and verapamil further enhanced significantly (P=0.004) this effect as compared to TLED alone. However, none of these treatments restored IDA to the level achieved in sensitive cells. Hyperthermia significantly increased IDA in the sensitive cell (P<0.05), whenever free-DNR or TLED was used, but had no significant effect in the resistant cells, suggesting that P-glycoprotein could efflux the additional drug uptaken in hyperthermic conditions. In all these experiments combining the use of a modulator (verapamil or TLED) and hyperthermia, IDA was statistically comparable to that achieved with free-DNR in sensitive cells at 37 degrees C, but still remained lower than the IDA in sensitive cells at 43 degrees C (P<0.05). The results also showed that hyperthermia affected the labelling of P-glycoprotein by MRK16 monoclonal antibody.