The NAMPT Inhibitor FK866 Increases Metformin Sensitivity in Pancreatic Cancer Cells.

ABSTRACT: Pancreatic cancer (pancreatic ductal adenocarcinoma: PDAC) is one of the most aggressive neoplastic diseases. Metformin use has been associated with reduced pancreatic cancer incidence and better survival in diabetics. Metformin has been shown to inhibit PDAC cells growth and survival, both in vitro and in vivo. However, clinical trials using metformin have failed to reduce pancreatic cancer progression in patients, raising important questions about molecular mechanisms that protect tumor cells from the antineoplastic activities of metformin. We confirmed that metformin acts through inhibition of mitochondrial complex I, decreasing the NAD⁺/NADH ratio, and that NAD⁺/NADH homeostasis determines metformin sensitivity in several cancer cell lines. Metabolites that can re

SUBMITTER: Parisotto M 

PROVIDER: S-EPMC9688551 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature