Abstract
Inflammatory reactions mediated by the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome contributes to non-small-cell lung cancer (NSCLC) progression, particularly in patients with bacterial infections. Salidroside (SAL) has recently been shown to suppress lipopolysaccharide- (LPS-) induced NSCLC proliferation and migration, but its mechanism of action remains unclear. It has been shown that SAL improves metabolic inflammation in diabetic rodents through AMP-activated protein kinase- (AMPK-) dependent inhibition of the NLRP3 inflammasome. However, whether the NLRP3 inflammasome is regulated by SAL in NSCLC cells and how its underlying mechanism(s) can be determined require clarification. In this study, human lung alveolar basal carcinoma epithelial (A549) cells were treated with LPS, and the effects of SAL on cell proliferation, migration, AMPK activity, reactive oxygen species (ROS) production, and NLRP3 inflammasome activation were investigated. We found that LPS induction increases the proliferation and migration of A549 cells which was suppressed by SAL. Moreover, SAL protected A549 cells against LPS-induced AMPK inhibition, ROS production, and NLRP3 inflammasome activation. Blocking AMPK using Compound C almost completely suppressed the beneficial effects of SAL. In summary, these results indicate that SAL suppresses the proliferation and migration of human lung cancer cells through AMPK-dependent NLRP3 inflammasome regulation.
Highlights
Lung cancer is the most fatal tumor globally, with estimates that by 2035, the disease will afflict more than 3 million individuals worldwide [1]
After Human lung alveolar basal carcinoma epithelial LPS (A549) cells were treated as described for 24 h (b) or 48 h (c), cell migration was determined through wound healing assays
Since LPS-induced NLRP3 inflammasome activation plays a critical role in the tumorigenesis of non-small-cell lung cancer (NSCLC) [10, 13], we investigated the effects of SAL on the NLRP3 inflammasome in LPS-treated A549 cells
Summary
Lung cancer is the most fatal tumor globally, with estimates that by 2035, the disease will afflict more than 3 million individuals worldwide [1]. Emerging evidence suggests that systemic inflammation contributes to tumorigenesis [4,5,6], including NSCLC [7]. In patients with lung cancer, concurrent bacterial infections enhance tumor progression [8] and increase mortality [9]. As the major pathogen in these cases, gram-negative bacteria negatively influence NSCLC through their effects on toll-like receptor- (TLR-) mediated inflammatory reactions, through the production of lipopolysaccharides (LPS) [8,9,10]. The LPS-stimulated production of proinflammatory cytokines in NSCLC can predict the clinical outcome in metastatic NSCLC patients [11]. Therapies that target LPS-induced inflammation can effectively ameliorate the adhesion and migration of NSCLC cells in vivo [10]
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