Adiponectin Suppresses Metastasis of Nasopharyngeal Carcinoma through Blocking the Activation of NF-κB and STAT3 Signaling

Abstract

Adiponectin is an adipocytokine with anti-inflammatory and anticancer properties. Our previous study has shown that blood adiponectin levels were inversely correlated to the risk of nasopharyngeal carcinoma (NPC), and that adiponectin could directly suppress the proliferation of NPC cells. However, the effect of adiponectin on NPC metastasis remains unknown. Here, we revealed in clinical studies that serum adiponectin level was inversely correlated with tumor stage, recurrence, and metastasis in NPC patients, and that low serum adiponectin level also correlates with poor metastasis-free survival. Coculture with recombinant adiponectin suppressed the migration and invasion of NPC cells as well as epithelial–mesenchymal transition (EMT). In addition, recombinant adiponectin dampened the activation of NF-κB and STAT3 signaling pathways induced by adipocyte-derived proinflammatory factors such as leptin, IL-6, and TNF-α. Pharmacological activation of adiponectin receptor through its specific agonist, AdipoRon, largely stalled the metastasis of NPC cells. Taken together, these findings demonstrated that adiponectin could not only regulate metabolism and inhibit cancer growth, but also suppress the metastasis of NPC. Pharmacological activation of adiponectin receptor may be a promising therapeutic strategy to stall NPC metastasis and extend patients’ survival.

Resistin Promotes Nasopharyngeal Carcinoma Metastasis through TLR4-Mediated Activation of p38 MAPK/NF-κB Signaling Pathway

“…The model of lung metastasis due to the 5-8F-Luc cells stably expressing luciferase was established as previously described [ 31 ]. After the modeling, mice were injected intravenously with 20 μg/kg resistin for 2 weeks; first for three consecutive days, and then injections were administrated every other day.…”

“…The wound-healing assay was performed as previously described [ 31 ]. The NPC cells were plated in 12-well culture plates, and cell confluence was 100% after adherence.…”

“…The migration and invasion assays were performed using 24-well Transwell inserts (BD Biosciences, San Jose, CA, USA) coated with or without growth factor-reduced Matrigel (Corning Incorporated, Corning, NY, USA), as previously described [ 31 ]. The cells were resuspended in a 200 ul serum-free medium that had been treated with or without resistin, which was added to the Transwell’s upper chamber, and a medium with 20% FBS was added to the Transwell’s lower chamber.…”

“…A Western blot analysis was performed as previously described [ 31 ]. Briefly, protein samples were extracted with radio-immunoprecipitation (RIPA) lysis buffer containing a protease inhibitor (Beyotime Biotechnology, Shanghai, China) and quantified with the bicinchoninic acid (BCA) protein assay kit (Beyotime Biotechnology).…”

“…Immunofluorescence staining was carried out as previously reported [ 31 ]. The NPC cells were cultured onto glass-bottom cell culture dishes (Wuxi NEST Biotechnology Co., Ltd., Jiangsu, China).…”