Metformin blocks the stimulative effect of a high-energy diet on colon carcinoma growth in vivo and is associated with reduced expression of fatty acid synthase

摘要: The molecular mechanisms responsible for the association of obesity with adverse colon cancer outcomes are poorly understood. We investigated effects a high-energy diet on growth an in vivo model. Seventeen days following injection 5!10 5 MC38 carcinoma cells, tumors from mice were approximately twice volume those control diet. These findings correlated observation that highenergy led to elevated insulin levels, phosphorylated AKT, and increased expression fatty acid synthase (FASN) by tumor cells. Metformin, antidiabetic drug, leads activation AMPK is currently under investigation its antineoplastic activity. observed metformin blocked effect growth, reduced attenuated phosphorylation AKT FASN. Furthermore, administration AMPK, inhibitory acetyl-CoA carboxylase, upregulation BNIP3 apoptosis as estimated poly (ADP-ribose) polymerase (PARP) cleavage. Prior work showed activating mutations PI3K associated outcome cancer; our results demonstrate aggressive behavior has similar this signaling pathway. demonstrated reverse diet, thus suggesting potential role agent management metabolically defined subset cancers. Endocrine-Related Cancer (2010) 17 351–360