Faculty Collaboration Database

Cyclooxygenase-2: potential role in regulation of drug efflux and multidrug resistance phenotype. Curr Pharm Des 2004;10(6):647-57

Date

02/18/2004

Pubmed ID

14965327

DOI

10.2174/1381612043453117

Scopus ID

2-s2.0-1442301504 (requires institutional sign-in at Scopus site)   92 Citations

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.

Author List

Sorokin A

Author

Andrey Sorokin PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

ATP-Binding Cassette Transporters
Animals
Apoptosis
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Humans
Inflammation
Isoenzymes
Membrane Proteins
Neoplasms
Phenotype
Prostaglandin-Endoperoxide Synthases