Download to Citation Manager

Cell Biology International (2010) 34, 21–25 (Printed in Great Britain)

Enhanced Full Text

PDF

Legacy HTML

Send to a friend

Add a comment

Review article

Cyclo-oxygenase 2 up-regulates the effect of multidrug resistance

Bing Liu*¹, Liyan Qu†¹ and Huimin Tao*²

*Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jie Fang Road, Hangzhou, 310009, Zhejiang, People's Republic of China, and †Department of Biochemistry and Molecular Biology, School of Medicine, Zhejiang University, #388 Yuhang Tang Road, Hangzhou, 310058, Zhejiang, People's Republic of China

COX-2 (cyclo-oxygenase 2), an inducible form of the enzyme that catalyses the first step in the synthesis of prostanoids, is associated with inflammatory diseases and carcinogenesis, which is suspected to promote angiogenesis and tissue invasion of tumours and resistance to apoptosis. COX-2 is also involved in drug resistance and poor prognosis of many neoplastic diseases or cancers. The activation of the COX-2/PGE₂ (prostaglandin E₂)/prostaglandin E receptor signal pathway can up-regulate the expression of all three ABC (ATP-binding-cassette) transporters, MDR1/P-gp (multidrug resistance/P-glycoprotein), MRP1 (multidrug-resistance protein 1) and BCRP (breast-cancer-resistance protein), which encode efflux pumps, playing important roles in the development of multidrug resistance. In addition, COX inhibitors inhibit the expression of MDR1/P-gp, MRP1 and BCRP and enhance the cytotoxicity of anticancer drugs. Therefore we can use the COX inhibitors to potentialize the effects of chemotherapeutic agents and reverse multidrug resistance to facilitate the patient who may benefit from addition of COX inhibitors to standard cytotoxic therapy.

Key words: breast-cancer-resistance protein (BCRP), cyclo-oxygenase 2 (COX-2), cyclo-oxygenase inhibitor, multidrug resistance/P-glycoprotein (MDR1/P-gp), multidrug-resistance protein 1 (MRP1)

Abbreviations: AA, arachidonic acid, ABC, ATP-binding-cassette, AC, adenylyl cyclase, BCRP, breast-cancer-resistance protein, COX, cyclo-oxygenase, cPGES, cytosolic PGE₂ synthase, EGR-1, early growth response factor 1, EP, prostaglandin E receptor, ERK, extracellular-signal-regulated kinase, MDR, multidrug resistance, mPGES, microsomal PGE₂ synthase, MRP, multidrug-resistance protein, NSAID, non-steroidal anti-inflammatory drug, PG, prostaglandin, P-gp, P-glycoprotein, PI3K, phosphoinositide 3-kinase, PKA, protein kinase A, PKB, protein kinase B, TXA₂, thromboxane A₂

¹These authors contributed equally to the present study.

²To whom correspondence should be addressed (email huimintao_zrgk@163.com).

Received 21 June 2009/14 August 2009; accepted 16 September 2009

Published online 16 December 2009, doi:10.1042/CBI20090129

© 2010 The Author(s) Journal compilation. © 2010 Portland Press Ltd