Ribociclib Inhibits P-gp-Mediated Multidrug Resistance in Human Epidermoid Carcinoma Cells.

ABSTRACT: The efficacy of cancer chemotherapy can be attenuated or abrogated by multidrug resistance (MDR) in cancer cells. In this study, we determined the effect of the CDK4/6 inhibitor, ribociclib (or LEE011), on P-glycoprotein (P-gp)-mediated MDR in the human epidermoid carcinoma MDR cell line, KB-C2, which is widely used for studying P-gp-mediated MDR in cancers. The incubation of KB-C2 cells with ribociclib (3-9 µM) increased the efficacy of colchicine, a substrate for P-gp. The cell expression of P-gp was down-regulated at both translation and transcription levels. Furthermore, ribociclib produced a 3.5-fold increase in the basal activity of P-gp ATPase, and the concentration required to increase basal activity by 50% (EC₅₀) was 0.04 μM. Docking studies indicated that ribociclib in

SUBMITTER: Zhang L 

PROVIDER: S-EPMC9016416 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature