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[Multidrug resistance of cancer cells mediated by ABC superfamily transporters].

ATP-binding cassette(ABC) superfamily transporters, including P-glycoprotein and MRP, actively transport various structurally dissimilar chemotherapeutic compounds out of cancer cells and confer multidrug resistance. Members of ABC superfamily which may extrude anti-cancer drugs are still expanding, thus the importance of these proteins are further increasing for cancer chemotherapy. Multidrug resistance will be acquired either by the induction of expression of ABC superfamily transporters or by mutations of ABC superfamily genes which cause amino acids substitutions. We recently found that amino acid substitutions in the first predicted transmembrane domain of P-glycoprotein increase the ability to confer resistance to important anti-cancer drugs adriamycin and VP-16. The mechanisms for drug recognition and transport of human P-glycoprotein and MRP are discussed.