Targeted doxorubicin-liposomes as a tool to circumvent P-gp-mediated resistance in ovarian carcinoma cells.

摘要

Resistance of tumor cells against chemo-therapeutics is a therapy-limiting obstacle. Several molecular mechanisms of chemoresis-tance have been identified. Amongst these, an increased efflux of chemotherapeutics by special transporters is a dominant phenomenon. The upregulation of P-glycoprotein (P-gp) is well known for multidrug resistance (MDR) by mediating a cellular efflux of several cyto-statics [3]. Doxorubicin is one of the most widely used drugs in chemotherapy. Furthermore, doxorubicin is successfully approved in a liposomal application form. The cyto-toxic effect results from blockade of nuclear DNA replication, which finally leads to apoptosis of tumor cells. However, doxorubicin activity is therapeutically limited by chemo-resistance which might, at least partly, be related to P-gp.