Adiponectin suppresses tumor growth of nasopharyngeal carcinoma through activating AMPK signaling pathway
AMPK
Male
AdipoRon
Nasopharyngeal Carcinoma
Research
R
Mice, Nude
Nasopharyngeal Neoplasms
AMP-Activated Protein Kinases
Xenograft Model Antitumor Assays
3. Good health
Mice
03 medical and health sciences
0302 clinical medicine
Case-Control Studies
Cell Line, Tumor
Nasopharyngeal carcinoma
Medicine
Animals
Humans
Adiponectin
Cell Proliferation
Signal Transduction
DOI:
10.1186/s12967-022-03283-0
Publication Date:
2022-02-14T12:03:03Z
AUTHORS (13)
ABSTRACT
Abstract
Background
Adiponectin is an adipocyte-secreted cytokine that enhances insulin sensitivity and attenuates inflammation. Although circulating adiponectin level is often inversely associated with several malignancies, its role in the development of nasopharyngeal carcinoma (NPC) remains unclear. Here, we investigated the clinical association between circulating adiponectin level and NPC, and examined the impact of adiponectin, as well as the underlying mechanisms, on NPC growth both in vitro and in vivo.
Methods
The association between circulating adiponectin level and the risk of developing NPC was assessed in two different cohorts, including a hospital-based case–control study with 152 cases and 132 controls, and a nested case–control study with 71 cases and 142 controls within a community-based NPC screening cohort. Tumor xenograft model, cell proliferation and cycle assays were applied to confirm the effects of adiponectin on NPC growth in cultured cells and in xenograft models. We also investigated the underlying signaling mechanisms with various specific pharmacological inhibitors and biochemistry analysis.
Results
High adiponectin levels were associated with a monotonic decreased trend of NPC risk among males in both the hospital-based case–control study and a nested case–control study. In vitro, recombinant human full-length adiponectin significantly inhibited NPC cell growth and arrested cell cycle, which were dependent on AMPK signaling pathway. The growth of xenograft of NPC tumor was sharply accelerated in the nude mice carrying genetic adiponectin deficiency. An adiponectin receptor agonist, AdipoRon, displayed strong anti-tumor activity in human xenograft models.
Conclusions
These findings demonstrated for the first time that circulating adiponectin is not only inversely associated with NPC, but also controls the development of NPC via AMPK signaling pathway. Stimulation of adiponectin function may become a novel therapeutic modality for NPC.
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CITATIONS (18)
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