PEDF inhibits non-small cell lung cancer proliferation by repressing autophagy through downregulating AMPK-ULK1 signaling

Abstract Background: Current investigations suggest that pigment epithelial factor (PEDF) can mediate progression of non-small cell lung cancer (NSCLC) by regulating autophagy. However, the underlying mechanisms associated with autophagy are still poorly known. This study aimed to investigate the relationship between PEDF-AMPK-ULK1 pathway and autophagy in NSCLCs.Methods: Intracellular autophagy was evaluated by some indicators, such as expression and activationof LC3-I, LC3-II and p62, distribution and number of autophagosomes observed by confocal microscopy. In addition, we also examined the activity and proliferative capacity of NSCLC cells under PEDF overexpression by CCK8, LDH assay and WB of related proteins. Results: The results show that PEDF could significantly inhibit NSCLC cell proliferation and cell viability, and increase LDH release and intercellular adhesion. Moreover, PEDF suppressed expression and activation of LC-3 and reduced the number and distribution of autophagosomes. PEDF-induced inhibition of autophagy showed a direct correlation with the suppressed proliferation capacity and cell viability of NSCLC cells. Western blot results showed that NSCLCs regulate autophagy through AMPK-ULK1 signaling pathway. PEDF can downregulate AMPK-ULK1 signaling pathway, and overexpression of AMPK or ULK1 can greatly reduce the inhibitory effect of PEDF on autophagy.Conclusions: PEDF could significantly inhibit the proliferative capacity and cell viability of NSCLCs, and the fundamental reason is that PEDF exerted an inhibitory function by regulating autophagy in NSCLCs. Finally, we elucidated that autophagy may be suppressed by inhibiting AMPK-ULK1 signaling pathway, thereby revealing a mechanism of lung cancer progression.