Metformin inhibits P-glycoprotein expression via the NF-κB pathway and CRE transcriptional activity through AMPK activation.

ABSTRACT:

Background and purpose

The expression of P-glycoprotein (P-gp), encoded by the multidrug resistance 1 (MDR1) gene, is associated with the emergence of the MDR phenotype in cancer cells. We investigated whether metformin (1,1-dimethylbiguanide hydrochloride) down-regulates MDR1 expression in MCF-7/adriamycin (MCF-7/adr) cells.

Experimental approach

MCF-7 and MCF-7/adr cells were incubated with metformin and changes in P-gp expression were determined at the mRNA, protein and functional level. Transient transfection assays were performed to assess its gene promoter activities, and immunoblot analysis to study its molecular mechanisms of action.

Key results

Metformin significantly inhibited MDR1 expression by blocking MDR1 gene transcription. Metformin also significantly

SUBMITTER: Kim HG 

PROVIDER: S-EPMC3051382 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature