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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Cyclooxygenase-2: Potential Role in Regulation of Drug Efflux and Multidrug Resistance Phenotype

Author(s): A. Sorokin

Volume 10 , Issue 6 , 2004

Page: [647 - 657] Pages: 11

DOI: 10.2174/1381612043453117

Price: $65

Abstract

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.

Keywords: cyclooxygenase, prostaglandins, P-glycoprotein, multidrug resistance, mdr1, renal mesangial, apoptosis, chemotherapeutic agents


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