Structurally diverse MDM2-p53 antagonists act as modulators of MDR-1 function in neuroblastoma.

ABSTRACT:

Background

A frequent mechanism of acquired multidrug resistance in human cancers is overexpression of ATP-binding cassette transporters such as the Multi-Drug Resistance Protein 1 (MDR-1). Nutlin-3, an MDM2-p53 antagonist, has previously been reported to be a competitive MDR-1 inhibitor.

Methods

This study assessed whether the structurally diverse MDM2-p53 antagonists, MI-63, NDD0005, and RG7388 are also able to modulate MDR-1 function, particularly in p53 mutant neuroblastoma cells, using XTT-based cell viability assays, western blotting, and liquid chromatography-mass spectrometry analysis.

Results

Verapamil and the MDM2-p53 antagonists potentiated vincristine-mediated growth inhibition in a concentration-dependent manner when used in combination with high MDR-1-ex

SUBMITTER: Chen L 

PROVIDER: S-EPMC4134492 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature