Table of Contents
New Journal of Science
Volume 2014, Article ID 476974, 10 pages
Review Article

Regulations of P-Glycoprotein/ABCB1/MDR1 in Human Cancer Cells

Division of Chemotherapy, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan

Received 9 January 2014; Accepted 25 April 2014; Published 20 May 2014

Academic Editor: Naoki Mori

Copyright © 2014 Kazuhiro Katayama et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Multidrug resistance (MDR) in cancer cells is a phenotype whereby cells display reduced sensitivity to anticancer drugs, based on a variety of mechanisms, including an increase in drug efflux, the reduction of drug uptake, the activation of cell growth and survival signaling, the promotion of DNA repair, and the inhibition of apoptosis signaling. Increased expression of the plasma membrane drug efflux pumps, the ATP-binding cassette (ABC) transporters, is involved in MDR. P-Glycoprotein/ABCB1 is a member of the ABC transporter family, and facilitates the efflux of various anticancer drugs, including anthracyclines, vinca alkaloids, epipodophyllotoxins, taxanes, and kinase inhibitors, from cells. P-Glycoprotein is also expressed in normal tissues and cells, including the kidney, liver, colon, and adrenal gland, to transport and/or secrete substrates and at the blood-brain, blood-placenta, and blood-testis barriers to protect these tissues from toxic substances. To understand the mechanistic functions of P-glycoprotein and to overcome MDR, investigators have identified the substrates and competitive inhibitors of P-glycoprotein. Recently, we and other groups reported associations between cellular signaling pathways and the expression, stability, degradation, localization, and activity of P-glycoprotein. The present review summarizes the currently available information about the transcriptional and posttranslational regulation of P-glycoprotein expression and function.