R
Roger
Guest
Curr Pharm Des. 2004;10(6):647-57.
Cyclooxygenase-2: potential role in regulation of drug efflux and multidrug resistance phenotype.
Sorokin A.
Department of Medicine, Division of Nephrology and Cardiovascular Research Center, Medical College
of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Multidrug resistance (MDR) of cancer cells to cytostatic agents is the major obstacle for the
succesfull chemotherapy. One of the causes of the development of cellular resistance to a wide
variety of drugs is the elevated expression of membrane transporter proteins such as members of ATP
binding cassette (ABC) protein superfamily. Expression of the ABC transporter MDR1, also termed P-
glycoprotein (P-gp), seems to correlate with drug resistance of tumors to chemotherapy. Cyclooxygenase-
2, an inducible isoform of enzyme, responsible for generation of prostaglandins from arachidonic
acid, is constitutively expressed in a number of cancer cells. Anti-cancer potency of cyclooxygenase
inhibitors is established, but the mechanism of Cox-2-dependent potentiation of tumor growth is a
subject of intense discussion. Here we focus on the discussion of potential link between Cox-2
expression and development of multidrug resistance phenotype. Our observation, that enforced
expression of Cox-2 causes enhancement in MDR1 expression and functional activity suggests the
existence of causal link between Cox-2 activity and MDR1 expression. The use of Cox-2 inhibitors to
decrease function of MDR1 may enhance accumulation of chemotherapy agents and decrease resistance of
tumors to chemotherapeutic drugs.
Cyclooxygenase-2: potential role in regulation of drug efflux and multidrug resistance phenotype.
Sorokin A.
Department of Medicine, Division of Nephrology and Cardiovascular Research Center, Medical College
of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Multidrug resistance (MDR) of cancer cells to cytostatic agents is the major obstacle for the
succesfull chemotherapy. One of the causes of the development of cellular resistance to a wide
variety of drugs is the elevated expression of membrane transporter proteins such as members of ATP
binding cassette (ABC) protein superfamily. Expression of the ABC transporter MDR1, also termed P-
glycoprotein (P-gp), seems to correlate with drug resistance of tumors to chemotherapy. Cyclooxygenase-
2, an inducible isoform of enzyme, responsible for generation of prostaglandins from arachidonic
acid, is constitutively expressed in a number of cancer cells. Anti-cancer potency of cyclooxygenase
inhibitors is established, but the mechanism of Cox-2-dependent potentiation of tumor growth is a
subject of intense discussion. Here we focus on the discussion of potential link between Cox-2
expression and development of multidrug resistance phenotype. Our observation, that enforced
expression of Cox-2 causes enhancement in MDR1 expression and functional activity suggests the
existence of causal link between Cox-2 activity and MDR1 expression. The use of Cox-2 inhibitors to
decrease function of MDR1 may enhance accumulation of chemotherapy agents and decrease resistance of
tumors to chemotherapeutic drugs.