Human Leptin Protein Induces Proliferation of A549 Cells via Inhibition of PKR-Like ER Kinase and Activating Transcription Factor-6 Mediated Apoptosis.
10.3349/ymj.2013.54.6.1407
- Author:
Qun LAI
1
;
Yan SUN
Author Information
1. Department of Thoracic Surgery, General Hospital of Zaozhuang Mining Group, Shandong, Zaozhuang, China. laiqunzz@yeah.net
- Publication Type:Original Article
- Keywords:
Apoptosis;
ER stress;
cell growth;
leptin;
TRAF2;
XPB1
- MeSH:
Activating Transcription Factor 6/genetics/*metabolism;
Apoptosis/*drug effects/genetics;
Blotting, Western;
Cell Line, Tumor;
Cell Proliferation/*drug effects;
Humans;
Leptin/*pharmacology;
Reverse Transcriptase Polymerase Chain Reaction;
eIF-2 Kinase/*metabolism
- From:Yonsei Medical Journal
2013;54(6):1407-1415
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: To investigate the anti-apoptotic mechanism of leptin in non-small cell lung cancer. MATERIALS AND METHODS: The influences of leptin on apoptosis were investigated, analyzing the mechanism that triggers growth of A549 cells. The effects of leptin on cell proliferation were examined by XTT analysis. Leptin, C/EBP homologous protein (CHOP), phosphorylated-PKR-like ER kinase (p-Perk), inositol requiring proteins-1, spliced X-box transcription factor-1 (XBP1), cleaved activating transcription factor-6 (ATF6), eukaryotic translation initiation factor-2alpha, caspase-12 and CHOP protein were detected in four groups by western blot, and endoplasmic reticulum (ER) stress related mRNA were detected by reverse transcription PCR. RESULTS: The expression of leptin in A549 and leptin transfected cells inhibited cisplatin activated ER stress-associated mRNA transcription and protein activation. Two ER stress unfolded protein response pathways, PERK and ATF6, were involved, and XBP1 and tumor necrosis factor receptor-associated factor 2 (TRAF2) were increased significantly when treated with cisplatin in A549-siRNA against leptin cells. Furthermore, CHOP expression was inhibited upon leptin expression in A549, LPT-PeP and LPT-EX cells. CONCLUSION: Leptin serves as an important factor that promotes the growth of A549 cells through blocking ER stress-mediated pathways. This blocking is triggered by p-Perk and ATF6 via inhibition of CHOP expression.
