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

Authors

  • Bing Liu,

    1. Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jie Fang Road, Hangzhou, 310009, Zhejiang, People's Republic of China
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    • These authors contributed equally to the present study.

  • Liyan Qu,

    1. Department of Biochemistry and Molecular Biology, School of Medicine, Zhejiang University, #388 Yuhang Tang Road, Hangzhou, 310058, Zhejiang, People's Republic of China
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    • These authors contributed equally to the present study.

  • Huimin Tao

    Corresponding author
    1. Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jie Fang Road, Hangzhou, 310009, Zhejiang, People's Republic of China
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email huimintao_zrgk@163.com

Abstract

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.

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