Related Experiment Video
Updated: Jul 24, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Selective modulation of P-glycoprotein-mediated drug resistance
M Bebawy1, M B Morris, B D Roufogalis
1Faculty of Pharmacy, The University of Sydney, N.S.W 2006, Australia.
Abstract:
Multidrug resistance associated with the overexpression of the multidrug transporter P-glycoprotein is a serious impediment to successful cancer treatment. We found that verapamil reversed resistance of CEM/VLB(100) cells to vinblastine and fluorescein-colchicine, but not to colchicine. Chlorpromazine reversed resistance to vinblastine but not to fluorescein-colchicine, and it increased resistance to colchicine. Initial influx rates of fluorescein-colchicine were similar in resistant and parental cells, whereas vinblastine uptake was about 10-fold lower in the resistant cells. These results provide indirect evidence that fluorescein-colchicine is transported from the inner leaflet of the membrane and vinblastine from the outer membrane leaflet. Verapamil inhibited fluorescein-colchicine transport in inside-out vesicles made from resistant cells, whilst chlorpromazine was found to activate the transport of fluorescein-colchicine. The chlorpromazine-induced activation of fluorescein-colchicine transport was temperature-dependent and may reflect its interaction with phospholipids localised in the same bilayer leaflet. Conversely, chlorpromazine localisation in this leaflet may be responsible for its allosteric inhibition of vinblastine transport from the opposing membrane leaflet. The proposed relationship between the selectivity of modulation of P-glycoprotein and the membrane localisation of the cytotoxic drug substrates and modulators may have important implications in the rational design of regimes for the circumvention of multidrug resistance clinically.
More Related Videos
08:59Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
Published on: December 11, 2017
14:51Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype
Published on: June 17, 2022
Related Concept Videos
Carrier-Mediated Transport
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Pharmacokinetics: Drug–Drug Interactions
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Drug Metabolism: Overview
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase