Cyclic-GMP-Elevating Agents Suppress Polyposis in Apc^Min mice by Targeting the Preneoplastic Epithelium.

ABSTRACT: The cGMP signaling axis has been implicated in the suppression of intestinal cancers, but the inhibitory mechanism and the extent to which this pathway can be targeted remains poorly understood. This study has tested the effect of cGMP-elevating agents on tumorigenesis in the Apc^Min/+ mouse model of intestinal cancer. Treatment of Apc^Min/+ mice with the receptor guanylyl-cyclase C (GCC) agonist linaclotide, or the phosphodiesterase-5 (PDE5) inhibitor sildenafil, significantly reduced the number of polyps per mouse (67% and 50%, respectively). Neither of the drugs affected mean polyp size, or the rates of apoptosis and proliferation. This was possibly due to increased PDE10 expression, as endogenous GCC ligands were not deficient in esta

SUBMITTER: Sharman SK 

PROVIDER: S-EPMC5811348 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature