PEDF inhibits non‑small cell lung cancer proliferation by suppressing autophagy through downregulation of AMPK‑ULK1 signaling

Miao,Haoran; Hui,Hongliang; Li,Huaming; Lin,Yangui; Li,Dan; Luo,Min; Jiang,Bo; Zhang,Yiqian

doi:10.3892/or.2022.8434

PEDF inhibits non‑small cell lung cancer proliferation by suppressing autophagy through downregulation of AMPK‑ULK1 signaling

Authors:
- Haoran Miao
- Hongliang Hui
- Huaming Li
- Yangui Lin
- Dan Li
- Min Luo
- Bo Jiang
- Yiqian Zhang
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Affiliations: Department of Thoracic Cardiovascular Surgery, The Eighth Affiliated Hospital of Sun Yat‑sen University, Shenzhen, Guangdong 518000, P.R. China, Community Health Center, The Eighth Affiliated Hospital of Sun Yat‑sen University, Shenzhen, Guangdong 518000, P.R. China
Published online on: October 24, 2022 https://doi.org/10.3892/or.2022.8434
Article Number: 219
Copyright : © Miao et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

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.

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