Current investigations suggest that pigment epithelial‑derived factor (PEDF) can mediate the progression of non‑small cell lung cancer (NSCLC) by regulating autophagy. However, the underlying mechanisms associated with autophagy remain poorly elucidated. The aim of the present study was to investigate the association between the PEDF/adenosine 5'‑monophosphate‑activated protein kinase (AMPK)/Unc‑51 like autophagy‑activated kinase 1 (ULK1) pathway and autophagy in NSCLC. Intracellular autophagy was evaluated using indicators such as the expression and activation of microtubule‑associated protein light chain 3‑I (LC3‑I), LC3‑II and p62, as well as the distribution and number of autophagosomes observed by confocal microscopy. In addition, the activity and proliferative capacity of NSCLC cells under PEDF overexpression was also examined using Cell Counting Kit‑8 and lactate dehydrogenase (LDH) assays, and western blotting (WB) of related proteins. The results revealed that PEDF significantly inhibited NSCLC cell proliferation and viability, and increased LDH release and intercellular adhesion. Furthermore, PEDF suppressed the expression and activation of LC‑3 and reduced the number and distribution of autophagosomes. The PEDF‑induced inhibition of autophagy exhibited a direct association with the suppressed proliferation capacity and cell viability of NSCLC cells. The results of WB showed that NSCLC cells regulated autophagy through the AMPK/ULK1 signaling pathway. PEDF downregulated the AMPK/ULK1 signaling pathway, and AMPK or ULK1 overexpression markedly reduced the inhibitory effect of PEDF on autophagy. In conclusion, PEDF overexpression significantly inhibited the proliferative capacity and cell viability of NSCLC cells, as PEDF exerted an inhibitory function by regulating autophagy in NSCLC cells. Finally, it was demonstrated that autophagy may be suppressed by inhibiting the AMPK/ULK1 signaling pathway, thereby revealing a mechanism of lung cancer progression.
Atherosclerosis remains a major cause of morbidity and mortality worldwide. Intraplaque neovascularization critically promotes atherosclerotic progression and instability. Vascular endothelial growth factor A (VEGFA) stimulates aberrant microvessel growth in plaques by inducing endothelial cell proliferation and migration. Pigment epithelium-derived factor (PEDF) potently inhibits VEGFA-dependent neovascularization. This study introduces a thermosensitive hydrogel (PFSgel) developed from poloxamer 407 (F127) and sodium alginate (SA) to deliver PEDF locally to atherosclerotic lesions. The PFSgel demonstrated a suitable liquid-solid transition at body temperature (37°C), then forming a stable 3D network structure after SA gelling with the Ca 2+ in the physiological environment which contributed to the character of controlled release. Rheological analysis confirmed its phase transition temperature of 28.7°C and notable self-healing properties, making it ideal for dynamic vascular environments. In vitro experiments showed that PFSgel could suppress VEGFA-induced endothelial cells’ proliferation and migration through modulation of CD31 and MMP-2/MMP-9 signaling. Notably, in vivo degradation test validated the controlled release pattern of PFSgel. In Apoe-deficient atherosclerotic mice, ultrasound-guided PFSgel injection onto the abdominal aorta enabled gradual in situ release of encapsulated PEDF. This effectively reduced plaque burden, neovascularization, and luminal stenosis, even with exogenous VEGFA administration. Histological analyses confirmed reduced lipid deposition, plaque area, and neovascularization within plaques. Overall, this novel in situ -forming PEDF delivery platform enables targeted suppression of pathological neovascularization via CD31 and MMP-2/MMP-9 pathways, representing a promising approach to stabilize high-risk plaques by intervening against VEGFA-dependent neovascularization.
危险品化学品经营许可证（带存储）