Atorvastatin inhibits pancreatic cancer cells proliferation and invasion likely by suppressing neurotrophin receptor signaling.

Abstract

BackgroundPancreatic cancer (PC) is aggressive and with poor clinical prognosis. However, mechanisms underlying the aggressiveness of PC remain unclear. Increasing evidence indicates that cholesterol, a major source of bio-energy, is required for the progression of human cancers including PC. Therefore, this study aimed to investigate the anti-tumor effect of atorvastatin, a widely used lipid-lowering agent that blocks the production of cholesterol, on human PC.MethodsWe firstly assessed the impacts of atorvastatin on the proliferation, apoptosis, cell cycle distribution, migration and invasion of human PC cells PANC-1 and SW1990. Furthermore, we studied the effects of atorvastatin on neurotrophin receptor signaling, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and their downstream receptors tropomyosin receptor kinase (Trk) Trk A, Trk B and Trk C in human PC cells.ResultsAtorvastatin significantly inhibited the proliferation, migration and invasion, and induced G1-phase cell cycle arrest and apoptosis in both PANC-1 and SW1990 cells. Meanwhile, atorvastatin treatment remarkably suppressed the expression of NGF, BDNF, and NT-3 as well as that of their downstream receptors Trk A and Trk C.ConclusionsThese results provide evidence that atorvastatin inhibits the proliferation, migration and invasion ability of human PC cells, and atorvastatin may exert the anti-tumor effect in PC via the inhibition of neurotrophin signaling pathway.