Expression of P-Glycoprotein in Normal and Malignant Rat Liver Cells (original) (raw)

1. C.H. Lee*,†,
2. G. Bradley*,‡, and
3. V. Ling*,†
4. *The Ontario Cancer Institute, Princess Margaret Hospital; †Department of Medical Biophysics, University of Toronto; ‡Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada, M4X 1K9

Excerpt

Resistance to multiple chemotherapeutic drugs is observed in many advanced human cancers. The molecular basis of such clinical resistance is not understood. One hypothesis is that subpopulations of malignant cells acquire a multidrug-resistant (MDR) phenotype during tumor progression and that such subpopulations have a survival advantage during chemotherapy leading to a nonresponsive disease. Different MDR mechanisms have been identified in cell lines and transplantable tumors (Morrow and Cowan 1990; Cole et al. 1992; Beck et al. 1993; Gottesman and Pastan 1993; Childs and Ling 1994). One of the best-characterized mechanisms involves the overexpression of the putative drug efflux pump, P-glycoprotein (Pgp) (Endicott and Ling 1989). Pgp has been shown to cause resistance to a variety of unrelated anticancer drugs such as the anthracyclines, the vinca-alkaloids, taxol, epipodophyllotoxins, dactinomycin, and some alkylating agents. Such drugs constitute a significant proportion of our anti-cancer drugs armamentarium. Thus, it is of interest to determine...