Metformin decreases glucose oxidation and increases the dependency of prostate cancer cells on reductive glutamine metabolism
Menée sur des lignées cellulaires et à l'aide d'un modèle murin, cette étude met en évidence des mécanismes permettant de rendre compte de l'association entre la prise de metformine et l'amélioration de la survie chez des patients atteints d'un cancer de la prostate
Metformin inhibits cancer cell proliferation and epidemiology studies suggest an association with increased survival in cancer patients taking metformin, however, the mechanism by which metformin improves cancer outcomes remains controversial. To explore how metformin might directly affect cancer cells, we analyzed how metformin altered the metabolism of prostate cancer cells and tumors. We found that metformin decreased glucose oxidation and increased dependency on reductive glutamine metabolism in both cancer cell lines and in a mouse model of prostate cancer. Inhibition of glutamine anaplerosis in the presence of metformin further attenuated proliferation while increasing glutamine metabolism rescued the proliferative defect induced by metformin. These data suggest that interfering with glutamine may synergize with metformin to improve outcomes in patients with prostate cancer.