Anticancer Mechanism of AP1 by Beta-catenin Mediated Cell Cycle Arrest in Human Gastric Cancer Cells

Abstract

The aim of this study was to determine the anticancer effects of AP1 in MKN-28 and AGS gastric cancer cells lines. Wnt/β-catenin signaling controls many aspects of cell behavior. One of its best-known and cancer-relevant functions is to promote cell cycle progression, and therefore proliferation, through transcriptional up-regulation of target genes such as those encoding c-MYC and cyclin D. The mechanism study showed that AP1 prompted down-regulated β-catenin expression level impeded cell proliferation, decreased cell population in cell cycle and reduced cell migration in vitro. The AP1 induced G1/S cell cycle arrest was characterized by down-regulation of cyclin-dependent kinase2 (CDK2), CDK6 expression and Cyclin D. AP1 not only induced cell cycle arrest, but also led to apoptotic cell death in gastric cancer cells. Activation of caspase-3, caspase-6 and caspase-7 was also observed. These data provide evidence that AP1 has the potential to be used in the treatment of gastric cancer.