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

Abstract

Background: Pancreatic 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. Methods: We 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. Results: Atorvastatin 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. Conclusions: These 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.