Inhibition of P-Glycoprotein Does Not Increase the Efficacy of Proteasome Inhibitors in Multiple Myeloma Cells.

ABSTRACT: P-Glycoprotein is a well-known drug transporter associated with chemotherapy resistance in a number of cancers, but its role in modulating proteasome inhibitor efficacy in multiple myeloma is not well understood. The second-generation proteasome inhibitor carfilzomib is thought to be a substrate of P-glycoprotein whose efficacy may correlate with P-glycoprotein activity; however, research concerning the first-in-class proteasome inhibitor bortezomib is inconsistent. We show that while P-glycoprotein gene expression increases with the disease stages leading to multiple myeloma it does not affect the survival of newly diagnosed patients treated with bortezomib. Moreover, RNA-seq on LP-1 cells demonstrated minimal basal P-glycoprotein expression which did not increase after exposure to bortez

SUBMITTER: Mynott RL 

PROVIDER: S-EPMC8033612 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature