Adiponectin, a circulating
peptide hormone produced in adipose tissue, has been shown to be reduced in the plasma of patients with
cancer, suggesting that this
adipokine may be mechanically involved in the pathogenesis of adiposity-related
carcinogenesis. In this study, we examined the expression of
adiponectin receptors (AdipoR1 and AdipoR2) and assessed the function of
adiponectin in
gastric cancer. All of the six
gastric cancer cell lines significantly expressed
mRNA and
protein of both receptors with variable levels. Addition of 30 microg/mL
adiponectin potently induced apoptosis and inhibited the proliferation of AZ521 and HCG27. Down-regulation of either AdipoR1 or AdipoR2 by specific
siRNA significantly suppressed the growth inhibitory effects of
adiponectin in both cell lines. Moreover, a local injection of
adiponectin markedly inhibited the growth of AZ521 inoculated subcutaneously in nude mice. Similarly, the continuous
intraperitoneal infusion of
adiponectin effectively suppressed the development of peritoneal
metastasis of AZ521.
Adiponectin negatively regulates the progression of
gastric cancer cells possibly through both AdipoR1 and AdipoR2. Although
adiponectin was already reported to have antiangiogenic effects, our results suggest that the antitumor effect of
adiponectin was, at least partially, dependent on the direct effects on
tumor cells.