Metformin suppresses Nrf2-mediated chemoresistance in hepatocellular carcinoma cells by increasing glycolysis.

ABSTRACT: The diabetes drug metformin has recently been shown to possess anti-cancer properties when used with other chemotherapeutic drugs. However, detailed mechanisms by which metformin improves cancer treatment are poorly understood. Here we provide evidence in HepG2 hepatocellular carcinoma cells that metformin sensitizes cisplatin-resistant HepG2 cells (HepG2/DDP) through increasing cellular glycolysis and suppressing Nrf2-dependent transcription. We show that metformin increases glucose uptake and enhances glucose metabolism through glycolytic pathway, resulting in elevated concentrations of intracellular NADPH and lactate. Consistently, high glucose medium suppresses Nrf2-dependent transcription and sensitizes HepG2/DDP cells to cisplatin. Elevated glycolysis was required for metformin to re

SUBMITTER: Cai L 

PROVIDER: S-EPMC7521529 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature