Adiponectin mediates antiproliferative and apoptotic responses in endometrial carcinoma by the AdipoRs/AMPK pathway

Abstract

ObjectiveDetermine the serum adiponectin levels in endometrial carcinoma (EC) cases and controls and explore the correlation between them. We assessed the functions of AdipoR1 and AdipoR2 in endometrial cancer cells to determine whether the AMPK/ERK and Akt pathways mediate the effects of adiponectin-induced apoptosis and anti-proliferation. Material and methodsThe serum adiponectin levels were measured via enzyme-linked immunosorbent assay (ELISA). The proliferation and apoptosis rates were determined with MTT and annexin V/PI assays. To evaluate the activation of AMPK, ERK, and Akt and the expression of Bcl-2 and Cyclin D1, western blot analysis was performed in Ishikawa 3-H-12 cells. We down-regulated AdipoRs by si-RNA to assess their functions. ResultsThe serum adiponectin levels were significantly decreased in patients with EC compared to controls. The adiponectin-induced apoptosis and anti-proliferation effects in EC cells were blocked by Compound C. Ishikawa 3-H-12 cells exhibited time- and dose-dependent increases in the p-AMPK levels after treatment with adiponectin. Adiponectin treatment reduced the levels of ERK and Akt phosphorylations and cyclin D1 and Bcl-2 mRNA and protein expression. Compound C blocked the effects on ERK, Akt, cyclin D1, and Bcl-2. AdipoR1 and AdipoR2 were involved in adiponectin-induced growth inhibition and ERK activation inhibition. We speculated that AdipoR1 has a greater role than adipoR2 in apoptosis and Akt activation inhibition after adiponectin treatment. ConclusionAdiponectin was an apoptotic and anti-proliferation agent for EC cells, and these effects were dependent on the AMPK/ERK and Akt pathways. AdipoR1 and AdipoR2 may play different roles in this process.