Reversal of Doxorubicin Resistance in Human Breast Adenocarcinoma (MCF-7) Cells by Liposomal Monensin
Annual summary rept. 1 Oct 2000-1 May 2005
FLORIDA AGRICULTURAL AND MECHANICAL UNIV TALLAHASSEE
Pagination or Media Count:
We have previously demonstrated that stealth monensin liposomes SML prepared by pH-gradient method enhance the cytotoxicity of doxorubicin by a factor of 16.5 in MCF-7dox cells. There was increase in MDR-1 and MRP-1 mRNA expression as a result of doxorubicin treatment, which was lowered by combination with SML. In the present study, enhancement of cytotoxic drugs by SML was reinvestigated. It showed that paclitaxel, etoposide and doxorubicin showed 2.8, 5.6 and 16.5 fold increase in cell kill in combination with SML. Caspase-3 assay to confirm apoptosis showed that, doxorubicin increased caspase-3 activity over control, but in combination with SML the activity was further increased by 2.1 fold. Fluorescence studies indicated that doxorubicin uptake was increased as a result of SML treatment. Also our studies indicated that the SML treatment lowered the efflux of doxorubicin from MCF-7dox cells. Finally in vivo animal experiments were conducted where nulnu mice were xenografted with MCF-7 cells. A group of animals received doxorubicin Smgkg i.v., while another group received SML 10-6 M doxorubicin treatments. Our results demonstrated that there were no significant differences between doxorubicin and SML doxorubicin treated mice for their tumor inhibition.
- Medicine and Medical Research