Modulation of P-Glycoprotein on Tumour Cells
A serious problem in cancer chemotherapy involves the generation of multidrug resistance (MDR). This phenomenon represents cross-resistance among a number of drugs, unrelated structurally or functionally, and is one of the major reasons for chemotherapy failure. MDR is associated to the overexpression of the mdr 1 gene which encodes a 170kDa plasma membrane glycoprotein known as P glycoprotein (Pgp) (Chen et al., 1986; Juliano and Ling, 1976; Riordan et al., 1985) and it has been demonstrated that overexpression of this protein is sufficient to confer cellular resistance (Ueda et al. 1987). Pgp functions as an ATP-dependent efflux pump capable of extruding antineoplastic agents to the outside of the cell reducing their intracellular levels. Structurally, Pgp is a transmembrane protein arranged in two homologous halves, each half containing an ATP binding site facing the cytoplasm, and with twelve hydrophobic regions forming the transmembrane loops (Gottesman and Pastan, 1993).
KeywordsNatural Killer Natural Killer Cell Multidrug Resistance K562 Cell Modulative Agent
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