Adiponectin pathway attenuates malignant mesothelioma cell growth

Kaijun Niu, Masanori Asada, Tatsuma Okazaki, Shinsuke Yamanda, Takae Ebihara, Hui Guo, Dongying Zhang, Ryoichi Nagatomi, Hiroyuki Arai, Masahiro Kohzuki, Satoru Ebihara

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Malignant mesothelioma (MM) is caused by exposure to asbestos. Because MM has a latency period, short survival time, and has a poor response to current therapeutic regimes, long-term preventive strategies are required to suppress the advance of pathological states after asbestos exposure. Accumulating evidence suggests that adiponectin plays a crucial role in the regulation of energy metabolism by increasing AMP-activated protein kinase (AMPK) activation. Several studies have indicated that the activation of AMPK decreases cyclooxygenase (COX)-2 expression. Because high COX-2 levels correlated with a worse prognosis and survival ratein MM, we examined whether the adiponectin pathway suppresses MM cell growth through the AMPK/COX-2 pathway. In vivo, dietary fishoil (a potential promoter of adiponectin) decreased the growth rate of MM, which was accompanied by an increase in adiponectin and phospho-AMPK levels, and a decrease in COX-2 level. In vitro, adiponectin significantly impaired the cell proliferation rate of MM cell lines. These effects partly involved induction of growth arrest and apoptosis to MM cells. MM cells expressed both adiponectin receptors 1 and 2 (AdipoR1 and -R2) at mRNA and proteins levels. These receptors were functional, because adiponectin activated AMPK. Adiponectin treatment also significantly down-regulated protein levels of COX-2 and its downstream prostaglandin E 2. Finally, inhibitory analysis of AdipoR1/R2 by small interfering RNA knockdown suggests that adiponectin enhances AMPK activity and impairs the cell proliferation rate of MM cells, mainly via AdipoR1. These findings suggest that the induction or supplementation of adiponectin is an important tactic for developing therapeutic strategies against MM.

Original languageEnglish
Pages (from-to)515-523
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume46
Issue number4
DOIs
Publication statusPublished - 2012 Apr

Keywords

  • AMP-activated protein kinase
  • Adiponectin
  • Cyclooxygenase-2
  • Fish oils
  • Malignant mesothelioma

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Adiponectin pathway attenuates malignant mesothelioma cell growth'. Together they form a unique fingerprint.

Cite this