The inhibitory effect of adiponectin on Caco‐2 cell proliferation

Abstract

Our previous work with the apcMin/+ (Min) mice suggests that loss of critical protective factor(s) from excessive loss of body fat on a high calcium diet results in increased intestinal tumor susceptibility. Since obesity is a risk factor for colon cancer and plasma adiponectin is inversely associated with obesity, we hypothesized that adiponectin may inhibit tumor proliferation, and that excessive loss of body fat in the already lean Min mice would lead to loss of this effect. Consequently, we utilized an in vitro coculture system to exam the effect of human adipocytes (HA) on the growth of Caco-2. Cell proliferation was measured by BrdU incorporation, DNA measurement and cell counts. HA substantially suppressed Caco-2 proliferation by 62.8% +10.1% (p=0.013). HA conditioned medium (CM) inhibited Caco-2 cell growth by 28.0%–65.6% (p<0.03) compared to DMEM. To investigate if adiponectin is responsible for this inhibitory effect, anti-human adiponectin-neutralizing antibody was added to the HACM and to the coculture system. The antibody blocked the growth-inhibiting effects in both HA and HACM. Similarly, a siRNA-mediated decrease in adiponectin protein in HA prevented the inhibitory effect of HA on the proliferation of Caco-2. These data indicate that adiponectin may suppress intestinal tumorigenesis and that loss of this effect in lipodystrophic min mice may be responsible for observed increases in tumor load.