Deprogramming metabolism in pancreatic cancer with a bi-functional GPR55 inhibitor and biased β₂ adrenergic agonist.

ABSTRACT: Metabolic reprogramming contributes to oncogenesis, tumor growth, and treatment resistance in pancreatic ductal adenocarcinoma (PDAC). Here we report the effects of (R,S')-4'-methoxy-1-naphthylfenoterol (MNF), a GPR55 antagonist and biased β₂-adrenergic receptor (β₂-AR) agonist on cellular signaling implicated in proliferation and metabolism in PDAC cells. The relative contribution of GPR55 and β₂-AR in (R,S')-MNF signaling was explored further in PANC-1 cells. Moreover, the effect of (R,S')-MNF on tumor growth was determined in a PANC-1 mouse xenograft model. PANC-1 cells treated with (R,S')-MNF showed marked attenuation in GPR55 signal transduction and function combined with increased β₂-AR/Gα_s/adenylyl cyclase/PKA signaling, both of

SUBMITTER: Wnorowski A 

PROVIDER: S-EPMC8901637 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature